FUNCTION OF M 3 MUSCARINIC RECEPTORS IN THE RAT URINARY BLADDER FOLLOWING PARTIAL OUTLET OBSTRUCTION
1999; Lippincott Williams & Wilkins; Volume: 161; Issue: 5 Linguagem: Inglês
10.1016/s0022-5347(05)68997-5
ISSN1527-3792
AutoresVLADIMIR P. KRICHEVSKY, Murali Pagala, IGOR VAYDOVSKY, VIJAYSINGH DAMER, Gilbert J. Wise,
Tópico(s)Neuropeptides and Animal Physiology
ResumoNo AccessJournal of UrologyInvestigative Urology1 May 1999FUNCTION OF M3 MUSCARINIC RECEPTORS IN THE RAT URINARY BLADDER FOLLOWING PARTIAL OUTLET OBSTRUCTION VLADIMIR P. KRICHEVSKY, MURALI K. PAGALA, IGOR VAYDOVSKY, VIJAYSINGH DAMER, and GILBERT J. WISE VLADIMIR P. KRICHEVSKYVLADIMIR P. KRICHEVSKY More articles by this author , MURALI K. PAGALAMURALI K. PAGALA More articles by this author , IGOR VAYDOVSKYIGOR VAYDOVSKY More articles by this author , VIJAYSINGH DAMERVIJAYSINGH DAMER More articles by this author , and GILBERT J. WISEGILBERT J. WISE More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)68997-5AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Partial outlet obstruction of the rat urinary bladder leads to hypertrophy and alteration in contractility of the detrusor muscle involving changes in muscarinic receptors. m3 muscarinic receptor subtype has been known to play a predominant role in contractility of normal urinary bladder. The purpose of the present study was to assess the role of m3 receptors in contractility of the obstructed bladder. Materials and Methods: In male rats, partial outlet obstruction of the urinary bladder was performed by surgically tying a 6-0 suture around the bladder neck, reducing the diameter of it by 2/3 of the original size. Four weeks after the surgery, the bladders were removed and thin strips were microdissected. Similarly, bladder strips from age matched unoperated normal rats were obtained. Sets of four strips from four normal or four obstructed rats were mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. The tension responses evoked by optimal electrical field stimulation at 1, 10, 30, 50, and 100 Hz, and the contracture responses evoked by 120 mM potassium and 0.01 to 300.0 micro M carbachol were recorded using a Nicolet digital oscilloscope. Similar responses were recorded in different sets of four strips following exposure to 10 and 100 nM 4-DAMP, which is a muscarinic antagonist with a high affinity for m3 and m1 receptor subtypes. Results: The obstructed bladders showed 119% increase in weight. In control physiological solution, the obstructed bladder strips did not show significant differences in electrically-evoked tension or carbachol contractures, but showed significantly lower potassium contractures compared with normal bladder strips. 4-DAMP at 10 to 100 nM significantly reduced the electrically evoked tension responses by about the same degree in normal and obstructed bladders, without affecting the potassium contractures. It significantly increased the EC50 values for carbachol contractures in normal bladder, and to a significantly lesser extent in obstructed bladder. Schild plots using the Hill transformed EC50 values showed that the pA (2) value for 4-DAMP was not significantly different in normal and obstructed bladders. Conclusions: Significantly smaller potassium contracture in the obstructed bladder indicates that depolarizability of the detrusor muscle membrane, and consequently the activity of voltage-gated Ca2+ channels may be reduced in the detrusor after partial outlet obstruction. Lack of a significant difference in the effect of 4-DAMP on the electrically evoked tension responses and in the pA2 values for 4-DAMP assessed by carbachol contractures, in normal and obstructed bladder strips, indicates that m3 muscarinic receptors still play a predominant role in causing detrusor contractility in the obstructed bladder, as in the normal bladder. References 1 : New York: Springer-Verlag1983. Google Scholar 2 : Detrusor response to outlet obstruction. World J. Urol.1984; 2: 208. Google Scholar 3 : Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction. J. Urol.1986; 136: 501. 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Google Scholar From the Urology Research Laboratory, Division of Urology, Maimonides Medical Center, Brooklyn, New YorkAccepted for publication October 12, 1998.(Krichevsky) Requests for reprints: Division of Urology, Maimonides Medical Center, 4802 Tenth Ave., Brooklyn, NY 11219.Supported by a grant from the Maimonides Research and Development Foundation.© 1999 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByPAGALA M, TETSOTI L, NAGPAL D and WISE G (2018) AGING EFFECTS ON CONTRACTILITY OF LONGITUDINAL AND CIRCULAR DETRUSOR AND TRIGONE OF RAT BLADDERJournal of Urology, VOL. 166, NO. 2, (721-727), Online publication date: 1-Aug-2001. Volume 161Issue 5May 1999Page: 1644-1650 Advertisement Copyright & Permissions© 1999 by American Urological Association, Inc.MetricsAuthor Information VLADIMIR P. KRICHEVSKY More articles by this author MURALI K. PAGALA More articles by this author IGOR VAYDOVSKY More articles by this author VIJAYSINGH DAMER More articles by this author GILBERT J. WISE More articles by this author Expand All Advertisement PDF DownloadLoading ...
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