Identification of c-kit-positive cells in the mouse ureter:the interstitial cel - 《American Journal of Physiology》美国生理学杂志干细胞之家



免疫细胞治疗专区	欢迎关注干细胞微信公众号

12 3 4 5 6 7 8 9 10 ... 27 下一页

返回列表

查看: 574833\|回复: 264	go Identification of c-kit-positive cells in the mouse ureter:the interstitial cel [复制链接]

轻羽

新手上路

Rank: 1

积分: 0
威望: 0
包包: 0

楼主

发表于 2009-4-21 13:36 |只看该作者 |倒序浏览 |打印

作者：Michael A.Pezzone, Simon C.Watkins, Sean M.Alber, William E.King, William C.de Groat, Michael B.Chancellor,  Matthew O.Fraser作者单位：1 Division of Gastroenterology, Hepatology, andNutrition, Department of Medicine, and Departments of Cell Biology and Physiology, Pharmacology, and Urology,University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania15213; and Division of Urology, Department ofSurgery, Duke University, Durh



                     7 v* P2 ]' h7 U" d  M* I

         . @8 ]; b+ w) Z- U4 L; R8 f

         * h3 K/ O" @  G- s" `
                  + f0 _: U: E  n# Q6 J
      # C/ w0 [4 f1 s; N6 ]% [+ R8 B
      2 l" |. L( I# A7 u& w
      2 M9 z! s! k: ^  Z
      【摘要】. E% B8 e6 d( l7 H0 ~6 q
   The existenceof a pacemaker system in the urinary tract capable of orchestrating themovement of filtrated urine from the ureteral pelvis to the distalureter and lower urinary tract seems intuitive. The coordinatedactivity necessary for such movement or "peristalsis" would likelyrequire an intricate network of cells with pacemaker-like activity, asis the case with the interstitial cells of Cajal (ICC) of the gut. Weinvestigated whether these putative pacemaker cells of the urinarytract are antigenically similar to ICC of the gut by usingimmunofluorescence staining for c-kit, a cell-surface marker specificfor ICC. Ureteral, urinary bladder, and urethral tissues were harvestedfrom female mice of the WBB6F1 strain, and fixed sections were preparedand stained for c-kit. Cell networks composed of stellate-appearing,c-kit-positive, ICC-like cells were found in the lamina propria and atthe interface of the inner longitudinal and outer circular musclelayers of the ureteral pelvis but not in the urinary bladder orurethra. Thus, like in the gut, c-kit-positive, ICC-like cells arepresent in the urinary tract but appear to be restricted to theproximal ureter of this murine species. 6 S3 T3 j: N; R8 V! I% m/ m  B( w
      【关键词】 urine urethral tissue pacemaker motility
   INTRODUCTION; F! T8 E- f  n  S

THE EXISTENCE OF apacemaker network capable of coordinating smooth muscle activity in theurinary tract has been previously proposed. The ureter, responsible forthe movement of urine from the kidney to the bladder, is thought tocontain pacemakers located in the renal pelvis that propagateelectrical activity distally giving rise to ureteral peristalsis( 6, 16, 17, 32, 47, 50, 60 ). Although electricalrecordings from the ureter demonstrate origination of the pacemakeractivity primarily from the proximal renal pelvis, pacemaker potentialshave been recorded from the upper, middle, and lower third of the humanureter ( 49 ). Further implicating a direct relationshipbetween smooth muscle contraction and electrical pacing, the actionpotentials following these pacemaker potentials were associated withintraureteral pressure increases.$ `2 ]/ z4 e* i  q; Q
# ]* }, Y1 t, x+ ]
Although myogenic and neurogenic mechanisms have been invoked for thegeneration and propagation of ureteral peristalsis, specialized cellswith both smooth muscle and neural properties may be involved. With theuse of histological techniques designed to identify such cells, Goslingand Dixon ( 16, 17 ) were the first to recognize specialized"atypical" smooth muscle cells confined to the upper urinary tract.These "atypical" smooth muscle cells closely apposed each other andtypical smooth muscle cells and were thought to be the reputedpacemaker cells. Klemm and Lang ( 30 ) found thishistologically defined, possible pacemaker-like network in the ureterpresent throughout the muscle layers, diminishing in cell numbersdistally along the ureter. Moreover, they found that the cellscomprising this pacemaker network were morphologically similar to thosepreviously described in the gut.6 X% S5 w. \1 h( G& a8 V
( ?$ C+ G5 k5 a
The selective identification and localization of interstitial cells ofCajal (ICC), the pacemaker cells of the gut, have been greatlyfacilitated by the discovery of their expression of the c-kit receptor.Specific antibodies to the c-kit receptor have been used to identifyICC in both animals ( 3, 26, 28, 39, 55, 58 ) and in humans( 27, 57 ). Local decreases in or lack of c-kitimmunoreactivity in the gut has been detected in human motilitydisorders such as Hirschsprungs's disease ( 57, 61 ) andintestinal pseudoobstruction ( 27 ). Mice with spontaneous mutations of the c-kit gene and deficient in ICC lack spontaneous slowwaves in the small intestine and have uncoordinated peristalsis ( 7 ). Similarly, the frequency and regularity of colonicperistaltic contractions were altered in such mice ( 39 ).: Y- {* j$ R9 q0 [/ s

In this study, the presence of ICC-like cell networks that may beresponsible for the generation of pacemaker activity in the urinarytract was investigated in mice using c-kit receptor immunofluorescence.Identification of the pacemaker system in the urinary tract and itsimplications for our present understanding of the neurophysiology ofthe urinary tract would be profound and may provide further insightinto a variety of important urological conditions.( ]# }( M# F: X6 t4 q) d+ K& t
$ @/ f. u2 l# i* r1 `$ w8 b
MATERIALS AND METHODS

Animals. Female WBB6F1 mice (Jackson Labs, Bar Harbor, ME), weighing 20-25g and 12-20 wk old, were housed in standard polypropylene cageswith ad libitum access to food and water in the University ofPittsburgh's Central Animal Facility. All studies were approved by theUniversity of Pittsburgh's Institutional Animal Care and Use Committeeand found to meet the standards for humane animal care and use as setby the Animal Welfare Act and the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Tissue processing. Mice were anesthetized with isoflurane (4%), and the ureters, urinarybladders, and urethras were harvested and immediately placed in 2%buffered paraformaldehyde for 1 h, cryoprotected in 30% sucrosein PBS overnight, and flash-frozen in liquid nitrogen-cooled isopentane. Tissues were cut in 8-µm frozen sections, mounted onpolylysine-coated slides, and kept frozen ( 20°C) untilimmunocytochemical processing.( w- ?/ B( K( T: W: w- I6 W

Immunocytochemistry. Tissue sections were rehydrated in KPBS at room temperature for 20 min,blocked with 10% normal goat serum for 20 min, and incubated overnightat 4°C with the primary antiserum, a rabbit polyclonal IgG antibodyto the human c-kit protein (Oncogene Research Products, Cambridge, MA),diluted 1:100 in KPBS, 0.05% goat serum and 0.1% Triton X-100. Thefollowing day, slides were rinsed with KPBS three times (10 min each)and then incubated with a Cy3-conjugated goat anti-rabbit IgG secondaryantibody (Jackson ImmunoResearch, West Grove, PA) at room temperaturefor 2 h at a dilution of 1:800 in KPBS, 0.05% goat serum, and0.1% Triton X-100. Because mast cells also contain the c-kit receptorand hence stain positive with c-kit antibodies, dual staining withfluorescein- avidin DCS (Vector Laboratories, Burlingame, CA) diluted1:200 for 2 h was used to specifically identify mast cellstaining. Slides were again washed three times (10 min each) with KPBSand coverslipped. Slides were imaged using an Olympus Fluoview 500 scanning confocal microscope in the Center for Biological Imaging atthe University of Pittsburgh.' h, h3 O" D# ?' f: P  C3 W
8 [$ M& ^0 r0 x+ x9 u5 ]
Controls for the specificity of the antisera consisted of incubation ofthe tissue with normal rabbit serum substituted for the primaryantiserum. With the use of this procedure, no nonspecific staining wasseen. The antibody concentrations and the optimal tissuepreparation used for immunofluorescence staining of c-kit in thismurine species had been previously determined in the intestine ( 39 ). Optimal antibody concentrations used in the urinarytract were determined by serial dilutions and are documented above.9 R5 |& e  K5 i: j' V

RESULTS+ A1 k+ J* q8 i

In Fig. 1, a confocal slice withdifferential interference contrast and fluorescence overlay depictsdual immunofluorescence staining of a section of proximal mouse ureter.In the lamina propria, note the network of red fluorescent,stellate-appearing cells that are c-kit positive. These c-kit-positivecells resembled ICC (ICC-like) and were negative for mast cell markers(FITC-avidin immunofluorescence). With the use of maximum-intensityprojection of the confocal stack, the c-kit-positive, ICC-like cellswere magnified and are depicted in Fig. 1 B.

Fig. 1. Confocal slice with differential interference contrast andfluorescence overlay of the proximal ureter of a female WBB6F1 mouse. A : network of interstitial cells of Cajal (ICC)-like cellsexpressing c-kit immunoreactivity is depicted in red fluorescence inthe lamina propria. The larger, yellowish-green-appearing granularcells staining positively for both FITC-avidin and c-kit are mastcells. Bar = 20 µm. B : high-power image of ICC-likecells offset from A using maximum-intensity projection ofconfocal stack. Bar = 10 µm.
0 W4 L& A. Y) o9 V+ L( B9 J
Networks of c-kit-positive, ICC-like cells were also localized adjacentto the inner longitudinal muscle fiber bundles and at the interface ofthe inner longitudinal and outer circular muscle layers (not shown).Furthermore, the c-kit-positive stellate cells were contiguous inserial tissue sections but limited to the ureteral pelvis and proximalureter. Such cells were not, however, found in either the urinarybladder or urethra.% a4 S& P$ }0 ?. r3 V1 ?
* B# j5 O2 P: |$ f/ o& z
Larger c-kit-positive cells were also noted in the lamina propria.Unlike the ICC-like cells, these larger cells also stained positivelyfor FITC-avidin and therefore appeared as yellow-green fluorescence asseen in Fig. 1 A. These immunohistological characteristics together with their intense granular morphology clearly characterized these cells as mast cells.
& {; q. ?: P$ R. e* [+ D) |
DISCUSSION
$ F+ V& e+ n9 f: }8 p4 ~* G
This study is the first to identify c-kit-positive, ICC-like cellsin the ureter that may be the putative pacemaker cells responsible forgeneration of ureteral peristalsis and the consequential movement ofurine from the kidney to the urinary bladder. The histologicaldistribution and cellular morphology of these c-kit-positive cells arecharacteristic of those cells previously identified as the ICC orpacemaker cells in the gastrointestinal tract. These findings furtherindirectly support the role of these identified cells as mediatorsand/or initiators of smooth muscle contraction in the tubularcomponents of the upper urinary tract. Recognition of abnormalities ofthe ICC-like system in the urinary tract may offer insight into avariety of important urological diseases, such as hydroureter andmegaloureter, which are congenital and/or acquired conditions thoughtto be a consequence of a deficiency in ureteral musculature innervation( 42 ).

An extensive review of the literature revealed few studies thatevaluated c-kit immunoreactivity in the genital urinary tract, and mosthave focused on the role of c-kit in gametogenesis in the testes( 11, 36, 38, 45 ). Most recently, Klemm et al. ( 29 ) comprehensively evaluated the cells underlyingpacemaker activity in the guinea pig upper urinary tract and foundcells morphologically similar to ICC cells, but they were notimmunoreactive for c-kit, the marker of ICC cells in the gut. Althoughc-kit-positive cells were present, they were morphologically consistentwith mast cells, the only other known c-kit-positive cell. The lack ofc-kit-positive ICC cells in Klemm's studies may be related to thespecies (guinea pig vs. mouse), the c-kit antibody used (murine vs.human), and/or the fixation methods, as we have found that ICC cellsare very sensitive to fixation methods.
, [* t3 u  D( _9 _. C4 O' ?
In a comprehensive evaluation of human tissue, Lammie et al.( 31 ) found scattered c-kit-positive immunoreactivity intransitional epithelial cells of the bladder and in mast cells of thebladder and gastrointestinal tract. Consistent with our results, they found no c-kit immunoreactivity in the urinary bladder smooth muscle,although they did report significant immunocytochemical localization ofkit ligand, the endogenous mast cell growth factor that binds to thec-kit receptor, both in the smooth muscle of the bladder and theintestines. This is not surprising, as the role of the bladder is oneof storage and intermittent expulsion. The lack of c-kit-positive,ICC-like cells in the mouse bladder stands in contrast to the recentreport of McCloskey and Gurney ( 35 ) where such cells wereidentified in the guinea pig bladder. Interestingly, the urinarybladder of the guinea pig also contains intramural autonomic ganglia( 15, 19, 62 ), in contrast to the murine bladder ( 15, 56 ). Given the association of ICC in the gut with intrinsicganglia and given that conditions of hypoganglionosis are alsoassociated with marked reductions in ICC ( 43 ), it seemsreasonable to propose that the lack of ICC in the mouse bladder is dueto a lack of intramural ganglia. With the use of this same line ofreasoning, one would predict that the human and cat bladder, which,like the guinea pig, both possess intramural urinary bladder ganglia( 40, 52, 53 ), would likewise possess ICC-like,c-kit-positive pacemaker cells. It has also been suggested that aurinary bladder network of intramural ganglia may contributefunctionally as an entity unto itself to both normal and pathologicalbladder function ( 9, 52 ), similarly, but to a lesserdegree than the enteric nervous system in the gut.3 |& b4 a# ~5 e% Q0 k  Y3 f

The urethra, which is also comprised by an outer circular and innerlongitudinal smooth muscle similar to the ureter ( 2 ), wasalso devoid of ICC-like cells in the present study. This was somewhatsurprising to us, as we previously observed peristaltic-like activityin in vitro whole mounted preparations of urethras from the rat(unpublished observations). It is tempting to speculate that eithersome other mechanism is responsible for pacemaker potential generationin the urethra, such as intrinisic smooth muscle tone responsible formaintaining continence with wave propagation via smooth muscle gapjunctions, or that our present histological protocols are, for someunknown reason, not allowing for the identification of ICC-like cellsin this organ.

Early studies investigating the neural input to the ureter and thepacemaker-like control of ureteral peristalsis focused oncatecholaminergic and cholinergic neural input to the ureter ( 8, 10, 13, 18, 37, 48 ). Follow-up studies, however, revealed thatthe adrenergic axons are preferentially distributed to the arterialvessels that supply the ureter rather than to the smooth muscle itself( 16, 59 ). With the later discovery of richcapsaicin-sensitive afferent input to the ureteral smooth musculature,a role of both substance P (SP) and calcitonin gene-related peptide(CGRP) containing afferent input has been implicated ( 12, 14, 23, 24, 46, 51, 54 ) with the latter neuropeptide found to be moreextensively represented ( 1, 46 ). These findings are alsoreflected in the subepithelial plexus of the ureter with ~90% of itsaxons being capsaicin-sensitive afferents ( 25, 46 ). Because the majority of the sensory fibers supplying the ureter are notactivated by physiological stimuli, they most likely signal noxiousstimuli ( 5 ) and may also regulate vascular and smooth muscle responses ( 22 ) to noxious stimuli by localefferent-like actions. On the other hand, direct physiological evidenceimplicating a role of CGRP containing afferent neurons in themodulation of ureteral peristalsis is apparent in studies which showedthat motility changes induced by electrical field stimulation aremainly mediated by CGRP ( 33, 34 ). Taken together, thesefindings suggest that CGRP in primary sensory axons of the ureter mayplay a role in modulation of ureteral smooth muscle activity and/or putative ureteral pacemaker cells rather than acting as the pacemaker system itself.
+ X$ [! `# _6 y+ |, A( J" c
Additional evidence supporting a relationship between afferentinnervation and c-kit expression is apparent in previous studies thatshowed that kit ligand is a neurotrophic factor for dorsal root ganglia(DRG) neurons, playing a role in neurite outgrowth and guiding axonsfrom the DRG ( 4, 21 ). Moreover, further characterizationof these c-kit-positive neurons in the DRG revealed that many (44%)contained SP, terminated in spinal cord laminae I and II, and werenerve growth factor responsive, further supporting their role asnociceptive C-fiber afferents ( 20 ). The importance andcomplexity of these interactions between sensory neurons and kit ligandare further evident in the finding that SP can induce production of kitligand, which, in turn, can upregulate SP receptors of the NK-1 subtypein bone marrow stroma ( 41 ).
: ?- h+ J: _& v7 a9 h! ^! \
Follow-up studies would be necessary to determine the functional roleof the c-kit-positive, ICC-like cells of the urinary tract.Physiological studies of ureteral peristalsis using techniques such asthose recently described by Roshani et al. ( 44 ) combined with immunocytochemical techniques in the commercially available c-kit-deficient mice would help define the direct role of these c-kit-positive, pacemaker-like cells in the urinary tract.
, q/ {3 D! m0 o7 w, C
In summary, we have identified cells in the proximal tubular componentsof the urinary tract with morphological and immunological phenotypessimilar to ICC pacemaker cells of the gut. We predict an abnormaldistribution of these ICC-like cells in the urinary tract may be auseful diagnostic marker of urinary tract diseases that involve theureter and may be useful in the planning of appropriate surgical orpharmacological interventions. Although the study of the role ofICC-like cells in urinary tract motility is in its infancy, moderntechnologies should facilitate rapid progress toward delineation of therole of these cells in normal physiology and pathological conditions.
* q* t% f" P/ K* X
ACKNOWLEDGEMENTS

Funding for this study was provided by National Institutes ofHealth Grant DK-02488 to M. A. Pezzone. Portions of this study were previously reported in abstract form at the 1999 annual meeting ofthe American Urological Association.
      【参考文献】
1. Amann, R,Skofitsch G,andLembeck F. Species-related differences in the capsaicin-sensitive innervation of the rat and guinea-pig ureter. Naunyn Schmiedebergs Arch Pharmacol 338:407-410,1988  .

2. Brading, AF. The physiology of the mammalian urinary outflow tract. Exp Physiol 84:215-221,1999 .6 y& _3 Y7 T+ {; n1 l

3. Burns, AJ,Lomax AEJ,Torihashi S,Sanders KM,andWard SM. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 93:12008-12013,1996 .

/ o2 H/ j* o3 w; t9 c
4. Carnahan, JF,Patel DR,andMiller JA. Stem cell factor is a neurotrophic factor for neural crest-derived chick sensory neurons. J Neurosci 14:1433-1440,1994 .2 u" s" ~) V* R. k! z7 |

5. Cervero, F,andSann H. Mechanically evoked responses of afferent fibres innervating the guinea-pig's ureter: an in vitro study. J Physiol 412:245-266,1989 .. L2 U+ g) H! |  v
' b8 ]: z# f  C/ W5 q

6. Constantinou, CE. Renal pelvic pacemaker control of ureteral peristaltic rate. Am J Physiol 226:1413-1419,1974 .2 K+ b+ P) V( N9 `. w$ ]$ r

7. Der-Silaphet, T,Malysz J,Hagel S,Larry Arsenault A,andHuizinga JD. Interstitial cells of cajal direct normal propulsive contractile activity in the mouse small intestine. Gastroenterology 114:724-736,1998  .
+ Z6 c; Z2 c* d% u

8. Dixon, JS,andGosling JA. Histochemical and electron microscopic observations on the innervation of the upper segment of the mammalian ureter. J Anat 110:57-66,1971  .
. [' K2 e) u! X2 z2 k
  h: X% J' p/ t& r+ b1 }

9. Drake, MJ,Mills IW,andGillespie JI. Model of peripheral autonomous modules and a myovesical plexus in normal and overactive bladder function. Lancet 358:401-403,2001  .; [, C# t6 z, {( K7 f
! h' ~$ S8 p' _) N0 Q' R1 t

" r" [7 _& R: \2 y) N' k& q( P
10. Duarte-Escalente, O,Labay P,andBoyarsky S. The neurohistochemistry of mammalian ureter: a new combination of histochemical procedures to demonstrate adrenergic, cholinergic, and chromaffin structures in ureter. J Urol 101:803-811,1969  .
4 [6 t4 r7 E% t! [
4 o( b$ f) @) O

11. Dym, M,Jia MC,Dirami G,Price JM,Rabin SJ,Mocchetti I,andRavindranath N. Expression of c-kit receptor and its autophosphorylation in immature rat type A spermatogonia. Biol Reprod 52:8-19,1995 .4 r; }. m* h8 P

12. Edyvane, KA,Smet PJ,Trussell DC,Jonavicius J,andMarshall VR. Patterns of neuronal colocalisation of tyrosine hydroxylase, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide and substance P in human ureter. J Auton Nerv Syst 48:241-255,1994  .
/ P: V. ^  V3 O6 r* W7 ~$ S  x
6 E4 \" L$ l" Q  y% l, p

13. Elbadawi, A,andSchenk EA. Innervation of the abdominopelvic ureter in the cat. Am J Anat 126:103-120,1969  .: {8 c; D8 a2 D5 r$ }. F
  E2 L7 \6 }! f7 {" O
5 }* L( d2 s% u# K0 D4 P

14. Franco-Cereceda, A,Henke H,Lundberg JM,Petermann JB,Hokfelt TH,andFischer JA. Calcitonin gene-related peptide (CGRP) in capsaicin-sensitive substance P-immunoreactive sensory neurons in animals and man: distribution and release by capsaicin. Peptides 8:399-410,1987  .+ d" L7 X; V  h' `

+ _  P+ {* z6 s$ q+ u

15. Gabella, G. Intramural neurons in the urinary bladder of the guinea-pig. Cell Tissue Res 261:231-237,1990  .
3 s5 n" g. X) `2 t
' u4 j% |4 M& a, _8 Y$ z1 y

16. Gosling, JA,andDixon JS. Species variation in the location of upper urinary tract pacemaker cells. Investig Urol (Berl) 11:418-423,1974.

8 |+ p$ Q5 F9 A
  O$ }: c' ?7 ^) X* u% a
17. Gosling, JA,andDixon JS. Structural evidence in support of an urinary tract pacemaker. Br J Urol 44:550-560,1972 .7 J# o  T4 r3 g3 d8 b

) t0 c+ ~" t- h: X7 z' P
3 j5 z0 A& X  V0 I# M5 ?
18. Gosling, JA,andDixon JS. The effect of 6-hydroxydopamine on nerves in the rat upper urinary tract. J Cell Sci 10:197-209,1972 ./ ^* U4 L! G* w4 S1 @  D$ t* L
1 t/ v/ U; D$ E; V$ }' q( p

! w. ~0 Y, E* t' O
19. Hanani, M,andMaudlej N. Intracellular recordings from intramural neurons in the guinea pig urinary bladder. J Neurophysiol 74:2358-2365,1995 .' t& p. ?- j6 C; E. C, ^) M. b

, ?% [: z  J4 z# k0 q$ C, K3 _* G
" o2 N0 P8 Y+ ~
20. Hirata, T,Kasugai T,Morii E,Hirota S,Nomura S,Fujisawa H,andKitamura Y. Characterization of c-kit-positive neurons in the dorsal root ganglion of the mouse. Dev Brain Res 85:201-211,1995 .- Q* ]3 Y( E2 ]  P3 h

7 T5 g9 d3 G3 s8 }+ D
21. Hirata, T,Morii E,Morimoto M,Kasugai T,Tsujimura T,Hirota S,Kanakura Y,Nomura S,andKitamura Y. Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos. Development 119:49-56,1993 .

( {( l0 D0 E, I" ]- ~( Z
$ D4 Z0 _' c$ E' |8 e/ A
22. Holzer, P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43:143-201,1991  ./ I6 X# j0 Q! O0 D

; K, J3 Q9 Q1 I6 N% z- R0 C
23. Holzer, P,Bucsics A,andLembeck F. Distribution of capsaicin-sensitive nerve fibres containing immunoreactive substance P in cutaneous and visceral tissues of the rat. Neurosci Lett 31:253-257,1982  .

  P$ f; i7 W6 M' n) ?
24. Hoyes, AD. Fine structure and response to capsaicin of primary afferent nociceptive axons in the rat and guinea-pig ureter.In: Sensory Receptor Mechanisms, edited by Hamann W,and Iggo A.. Singapore: World Scientific, 1984, p. 25-34.  x& n* O4 ~/ R7 y
$ o4 J, N  H. J& J. j
! v8 b! _  t6 C& I3 o2 f% C
  B! b+ Y7 B* g  I$ S- z
25. Hoyes, AD,andBarber P. Degeneration of axons in the ureteric and duodenal nerve plexuses of the adult rat following in vivo treatment with capsaicin. Neurosci Lett 25:19-24,1981  .  h  j7 ~2 [* Z2 Q( s. G
! Y; U/ f/ ~  q6 V
) g; o1 w& N" ]8 t+ N- E# q' \: v
# Z4 c8 }6 S# o6 J* O5 k
26. Huizinga, JD,Thuneberg L,Kluppel M,Malysz J,Mikkelsen HB,andBernstein A. W/Kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373:347-349,1995 .

27. Isozaki, K,Hirota S,Miyagawa JI,Taniguchi M,Shinomura Y,andMatsuzawa Y. Deficiency of c-kit cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol 92:332-334,1997  .: Z2 u, G2 r) p7 [' {
3 E) t9 e/ [4 A" `

: B3 R! D4 B; y' ?
28. Isozaki, K,Hirota S,Nakama A,Miyagawa JI,Sinomura Y,Xu Z,Nomura S,andKitamura Y. Disturbed intestinal movement, bile reflux to the stomach and deficiency of c-kit-expressing cells in Ws/Ws mutant rats. Gastroenterology 109:456-464,1995  .* s5 @) t9 o1 p" @' e, u# M( I

" }4 ~" Z2 o- t' D6 `: q
6 u, ^2 x/ F5 G  F0 w  {! v/ ?- s
29. Klemm, MF,Exintaris B,andLang RJ. Identification of the cells underlying pacemaker activity in the guinea-pig upper urinary tract. J Physiol 519:867-884,1999 .- t) I1 x4 I! P  d2 T  Y

0 ~6 \# o) R, e9 f1 k" K& Q" \
30. Klemm, MF,andLang RJ. Morphological characterization of guinea pig upper urinary tract (Abstract). Proc Aust Neurosci Soc 9:87,1998., v6 Q# }3 ]+ D
* }" ]( N" x4 V' P: h' C$ i, X

$ o9 a6 R  v+ U; ]$ a
31. Lammie, A,Drobnjak M,Gerald W,Saad A,Cote R,andCordon-Cardo C. Expression of c-kit and kit ligand proteins in normal human tissues. J Histochem Cytochem 42:1417-1425,1994 .
( h$ x! k/ A9 a5 r

) N" ~; }$ h( a! U* I) r9 q
32. Lang, RJ,Exintaris B,Teele ME,Harvey J,andKlemm MF. Electrical basis of peristalsis in the mammalian upper urinary tract. Clin Exp Pharmacol Physiol 25:310-321,1998  .

33. Maggi, CA,andGiuliani S. The neurotransmitter role of calcitonin gene-related peptide in the rat and guinea pig ureter: effect of a calcitonin gene-related peptide antagonist and species-related differences in the action of omega conotoxin on calcitonin gene-related peptide release from primary afferents. Neuroscience 43:261-268,1991  .* z0 m) x5 _! i0 Y, p/ {. s
+ b+ W; e. C& d2 O2 Q* V% m

34. Maggi, CA,Santicioli P,Giuliani S,Abelli L,andMeli A. The motor effect of the capsaicin-sensitive inhibitory innervation of the rat ureter. Eur J Pharmacol 126:333-336,1986  .$ K+ B2 y- L9 e- ^# `7 _3 ?! Q4 e

7 u4 e* m6 g2 S2 Z9 }" O9 L
35. McCloskey, KD,andGurney AM. Kit positive cells in the guinea pig bladder. J Urol 168:832-836,2002  .
8 J( _4 j" @* z6 d

36. Munsie, M,Schlatt S,deKretser DM,andLoveland KL. Expression of stem cell factor in the postnatal rat testis. Mol Reprod Dev 47:19-25,1997  .9 v) O' o- ?7 k1 H5 c! l

# C' V, H% {+ {" o. h' c
37. Ogata, J,Ueno F,Sakata T,andYamasaki K. Histochemical study of adrenergic and cholinergic nerve fibers in the dog ureter. Kumamoto Med J 26:113-119,1973 .* B1 `) e9 [7 l, {; j' t( R

38. Orth, JM,Jester WF,andQiu J. Gonocytes in testes of neonatal rats express the c-kit gene. Mol Reprod Dev 45:123-131,1996  .

- d7 `& _5 C& b( R5 H9 ^2 Q
39. Pezzone, MA,Fraser MO,VanBibber MM,andde Groat WC. Physiologic evaluation of colonic motility in awake c-kit deficient mice and immunofluorescence evaluation of colonic interstitial cells of Cajal.In: Neurogastroenterology From the Basics to the Clinics, edited by Krammer HJ,and Singer MV.. London: Kluwer, 2000, p. 461-469.
( b1 H' ^$ X0 |" d. a
8 N% ]  m$ s% {. X. _, @
  Y% s/ C" A9 O4 I& t6 N$ o* P
40. Pushkarev Iu, P,andKalganova MA. The functional properties of the intramural bladder neural plexus. Fiziol Zh 76:1465-1469,1990.

41. Rameshwar, P,andGascon P. Substance P (SP) mediates production of stem cell factor and interleukin-1 in bone marrow stroma: potential autoregulatory role for these cytokines in SP receptor expression and induction. Blood 86:482-490,1995 .

42. Robbins, SL,Cotran RS,andKumar V. The lower urinary tract.In: Pathologic Basis of Disease (3rd ed.), edited by Robbins SL,Cotran RS,and Kumar V.. Philadelphia, PA: Saunders, 1984, p. 1062-1080.' r( M* {6 n1 t, Y2 c9 f& g

4 n( ?" T  O- b, R5 v# L9 L4 x
43. Rolle, U,Piotrowska AP,Nemeth L,andPuri P. Altered distribution of interstitial cells of Cajal in Hirschsprung disease. Arch Pathol Lab Med 126:928-933,2002  .

" f8 V* b0 i' X) [8 E7 H; `

44. Roshani, H,Dabhoiwala NF,Tee S,Dijkhuis T,Kurth KH,Ongerboer de Visser BW,de Jong JMBV,andLamers WH. A study of ureteric peristalsis using a single catheter to record EMG, impedance, and pressure changes. Tech Urol 5:61-66,1999 .
3 e: ^+ A7 p, ^& ?
# T1 a" V6 @, [/ q* i/ y* e3 Q8 w

45. Sandlow, JI,Feng HL,andSandra A. Localization and expression of the c-kit receptor protein in human and rodent testis and sperm. Urology 49:494-500,1997  .4 m5 U1 z9 P" R" @

9 a0 G* u* B# R2 k

46. Sann, H,Jancso G,Ambrus A,andPierau FK. Capsaicin treatment induces selective sensory degeneration and increased sympathetic innervation in the rat ureter. Neuroscience 67:953-966,1995  .2 Q: x4 K  Z( d1 E

4 x- S% V9 c% t. Y2 g1 S
- e! I8 J, M6 d5 t6 |
47. Santicioli, P,andMaggi CA. Myogenic and neurogenic factors in the control of pyeloureteral motility and ureteral peristalsis. Pharmacol Rev 50:683-721,1998 .* h0 p2 O7 w6 {9 f7 @  j+ {

& A. Y. r6 p" R/ A
48. Schulman, CC,Duarte-Escalent O,andBoyarsky S. The ureterovesical innervation. A new concept based on a histochemical study. Br J Urol 44:698-712,1972 .* N! g/ N* H9 }/ _7 {4 F6 M

" `$ ]9 d* z2 h7 U* ^7 N
# V1 s% E5 ^( A' ~# @. Y( N
49. Shafik, A. Electroureterogram: human study of the electromechanical activity of the ureter. Urology 48:696-699,1996  .0 @) ]) w2 l$ N$ a. _$ q4 F3 I
. s& |+ {& o( e- G

50. Shiratori, T,andKinoshita H. Electromyographic studies on the urinary tract. II. Electromyographic study on the genesis of peristaltic movement of the dog's ureter. Tohoku J Exp Med 73:103-108,1961.1 Z8 q8 z0 S" U: }4 i/ ]0 d) V
3 s! W) m* k; v( g

51. Sikri, KL,Hoyes AD,Barber P,andJagessar H. Substance P-like immunoreactivity in the intramural nerve plexuses of the guinea-pig ureter: a light and electron microscopical study. J Anat 133:425-442,1981  .

0 Q' R* |+ b/ }* u  U9 X0 B6 n

52. Smet, PJ,Jonaviciius J,Marshall VR,andDe Vente J. Distribution of nitric oxide sythase-immunoreactive nerves and identification of the cellular targets of nitric oxide in guinea-pig and human urinary bladder by cGMP immunohistochemistry. Neuroscience 71:337-348,1996  .' @  p) x" A. V; `: R
2 a0 w: |  M; e, s# D) X+ j8 s

' i  ]; q4 y: R" Q9 e  c  m
53. Smet, PJ,Moore KH,andJonavicius J. Distribution and colocalization of calcitonin gene-related peptide, tachykinins, and vasoactive intestinal peptide in normal and idiopathic unstable urinary bladder. Lab Invest 77:37-49,1997 .

4 J6 U% v% ?& j* z; E
% b1 P) E# D+ H2 q8 p( u8 Q8 q  d. |
54. Su, HC,Wharton J,Polak JM,Mulderry PK,Ghatei MA,Gibson SJ,Terenght G,Morrison JFB,Ballesta J,andBloom SR. Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: combined retrograde tracing and immunohistochemistry. Neurosci Lett 18:727-747,1986.9 T, Q2 c1 |, A' F+ I0 H

- i7 }0 n+ _. O- w1 U0 C
8 C$ v9 H5 y6 E9 Z0 B
55. Torihashi, S,Ward SM,Nishikawa S,Nishi K,Kobayashi S,andSanders KM. C-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res 280:97-111,1995  .  [8 Z- j# Q' a! @7 O6 B

: ^/ u. |1 o' v; c! }
56. Uvelius, B,andGabella G. Intramural neurones appear in the urinary bladder wall following excision of the pelvic ganglion in the rat. Neuroreport 6:2213-2216,1995  .- g8 U" Q7 X5 d1 g# {3 X
' \% v. _! \# O/ V, p$ T

( {4 i" Z0 N+ O* n: P
57. Vanderwinden, JM,Rumessen JJ,Liu H,Descamps D,De Laet MH,andVanderhaeghen JJ. Interstitial cells of Cajal in human colon and in Hirschsprung's disease. Gastroenterology 111:901-910,1996  .1 ^6 L% i* v1 w3 Z! u$ r

2 [1 _" d& T. T9 Z' U3 v( A

58. Ward, SM,Burns AJ,Torihashi S,andSanders KM. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol 480:91-97,1994 .

. G: o# ]1 l1 g6 ^/ ~7 q7 @- k

59. Wein, AJ,Leoni JV,Schoenberg HW,andJacobowitz D. A study of the adrenergic nerves in the dog ureter. J Urol 108:232-233,1972  .
, V" X  _2 O: H& s. L" a
/ \0 @& ]3 S6 }7 K  t# \# R. p) X' r3 v$ B
) g( l" g2 }+ v
60. Weiss, RM,Wagner ML,andHoffman BF. Localization of the pacemaker for peristalsis in the intact canine ureter. Investig Urol (Berl) 5:42-46,1967.
/ }4 D0 p) X; H3 Y' W/ f6 ^1 j$ Q; z

61. Yamataka, A,Kato Y,Tibboel D,Murata N,Sueyoshi N,Fujimoto T,Nishiye H,andMiyano T. A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung's Disease. J Pediatr Surg 30:441-444,1995  .

62. Zhou, Y,andLing EA. Colocalization of nitric oxide synthase and some neurotransmitters in the intramural ganglia of the guinea pig urinary bladder. J Comp Neurol 394:496-505,1998  .

收藏0 分享0 顶0 踩0