Abstract
Interstitial cells of Cajal (ICC) evoke pacemaker activities in many tissues. The purpose of this study was to investigate the relationship between interstitial cell and pacemaker activity in the human ureter through the recording of spontaneous contractions. Spontaneous contractions of eight circular and longitudinal smooth muscle strips of the human ureter to acetylcholine (ACh) and/or norepinephrine (NE) were observed. Human ureteral strips were divided into proximal and distal groups, and each group was subdivided into circular and longitudinal groups. The proximal group showed spontaneous activities of 3∼4 times within 5 minutes in the longitudinal group. ACh (10–4 M) augmented the frequency of the spontaneous contractions. The cumulative application of NE also augmented the frequency in a dose-dependent manner. The effects of NE application were inhibited by concomitant application of 10–5 M glibenclamide. Receptor tyrosine kinase (c-kit) staining revealed abundant ICCs only in proximal tissues. Therefore, spontaneous contractions of the human ureter might be modulated by ICC in the proximal region, and the actions might be related with the activation of cholinergic and/or adrenergic system mediated by a glibenclamide-sensitive pathway.
References
1. Cajal SR. Histologie du système nerveux de l'homme et des vertébrés. Paris, Maloine. 1911; 2:891–942.
2. Langton P, Ward SM, Carl A, Norell MA, Sanders KM. Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon. Proc Natl Acad Sci U S A. 1989; 86:7280–7284.
3. Ward SM, Burns AJ, Torihashi S, Sanders KM. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol. 1994; 480:91–97.
4. McCloskey KD, Gurney AM. Kit positive cells in the guinea pig bladder. J Urol. 2002; 168:832–836.
5. Biers SM, Reynard JM, Doore T, Brading AF. The functional effects of a c-kit tyrosine inhibitor on guinea-pig and human detrusor. BJU Int. 2006; 97:612–616.
6. Metzger R, Schuster T, Till H, Stehr M, Franke FE, Dietz HG. Cajal-like cells in the human upper urinary tract. J Urol. 2004; 172:769–772.
7. Torihashi S, Ward SM, Nishikawa S, Nishi K, Kobayashi S, Sanders KM. c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res. 1995; 280:97–111.
8. Pezzone MA, Watkins SC, Alber SM, King WE, de Groat WC, Chancellor MB, Fraser MO. Identification of c-kit-positive cells in the mouse ureter: the interstitial cells of Cajal of the urinary tract. Am J Physiol Renal Physiol. 2003; 284:F925–F929.
9. Isozaki K, Hirota S, Miyagawa J, Taniguchi M, Shinomura Y, Matsuzawa Y. Deficiency of c-kit+ cells in patients with a myopathic form of chronic idiopathic intestinal pseudoobstruction. Am J Gastroenterol. 1997; 92:332–334.
10. Vanderwinden JM, Rumessen JJ. Interstitial cells of Cajal in human gut and gastrointestinal disease. Microsc Res Tech. 1999; 47:344–360.
11. Yamataka A, Kato Y, Tibboel D, Murata Y, Sueyoshi N, Fujimoto T, Nishiye H, Miyano T. A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung's disease. J Pediatr Surg. 1995; 30:441–444.
12. Kim JK, Han WH, Lee MY, Myung SC, Kim SC, Kim MK. Testosterone relaxes rabbit seminal vesicle by calcium channel inhibition. Korean J Physiol Pharmacol. 2008; 12:73–77.
13. Ogasawara N, Tsukamoto T, Inada K, Mizoshita T, Ban N, Yamao K, Joh T, Itoh M, Tatematsu M. Frequent c-Kit gene mutations not only in gastrointestinal stromal tumors but also in interstitial cells of Cajal in surrounding normal mucosa. Cancer Lett. 2005; 230:199–210.
14. Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature. 1994; 372:231–236.
15. Hille B. Ionic channels of excitable membranes. 1st ed.Sinauer: Sunderland;c;1992. p. 119–244.
16. Park SY, Lee MY, Keum EM, Myung SC, Kim SC. Ionic currents in single smooth muscle cells of the human vas deferens. J Urol. 2004; 172:628–633.
17. Jun JY, Choi S, Yeum CH, Chang IY, Park CK, Kim MY, Kong ID, So I, Kim KW, You HJ. N oradrenaline inhibits pacemaker currents through stimulation of beta 1-adrenoceptors in cultured interstitial cells of Cajal from murine small intestine. Br J Pharmacol. 2004; 141:670–677.
18. Oostendorp J, Preitner F, Moffatt J, Jimenez M, Giacobino JP, Molenaar P, Kaumann AJ. Contribution of beta-adrenoceptor subtypes to relaxation of colon and oesophagus and pacemaker activity of ureter in wildtype and beta(3)-adrenoceptor knockout mice. Br J Pharmacol. 2000; 130:747–758.
19. Satoh H. Effects of ATP-sensitive K+ channel openers on pacemaker activity in isolated single rabbit sino-atrial node cells. J Cardiovasc Pharmacol. 1993; 22:863–868.
20. Hatton WJ, Mason HS, Carl A, Doherty P, Latten MJ, Kenyon JL, Sanders KM, Horowitz B. Functional and molecular expression of a voltage-dependent K(+) channel (Kv1.1) in interstitial cells of Cajal. J Physiol. 2001; 533:315–327.
21. Narishige T, Egashira K, Akatsuka Y, Katsuda Y, Numaguchi K, Sakata M, Takeshita A. Glibenclamide, a putative ATP-sensitive K+ channel blocker, inhibits coronary autoregulation in anesthetized dogs. Circ Res. 1993; 73:771–776.
22. Pfister SL, Pratt PE, Kurian J, Campbell WB. Glibenclamide inhibits thromboxane-mediated vasoconstriction by thromboxane receptor blockade. Vascul Pharmacol. 2004; 40:285–292.