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Am J Physiol Regul Integr Comp Physiol 297: R1486-R1493, 2009. First published September 9, 2009; doi:10.1152/ajpregu.90516.2008
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Articles

Functional significance of muscarinic receptor expression within the proximal and distal rat vagina

Maureen Basha,1,2 Edward F. LaBelle,2 Gina M. Northington,3 Tanchun Wang,1 Alan J. Wein,2 and Samuel Chacko2

1Department of Pharmacology and Physiology, Drexel University College of Medicine; Philadelphia; 2Department of Surgery, Division of Urology, University of Pennsylvania School of Medicine, Philadelphia; and 3Department of Obstetrics and Gynecology, Division of Urogynecology and Reconstructive Pelvic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania/

Submitted June 18, 2008 ; accepted in final form September 3, 2009

Information regarding the role of cholinergic nerves in mediating vaginal smooth muscle contraction is sparse, and in vitro studies of the effects of muscarinic agonists on vaginal smooth muscle are discrepant. The goal of this study was to determine the expression of muscarinic receptors in the vaginal wall of the rat. In addition, we sought to determine the effect of the muscarinic receptor agonist carbachol on contractility and inositol phosphate production of the proximal and distal rat vaginal muscularis. RT-PCR analysis indicated that both M2 and M3 receptor transcripts were expressed within the proximal and distal rat vagina. Carbachol dose-dependently (10–7–10–4 M) contracted the rat vaginal muscularis with a greater maximal contractile response in the proximal vagina (P < 0.01) compared with the distal vagina. The contractile responses of the rat vaginal muscularis to carbachol were dose dependently inhibited by the M3 antagonist para-fluoro-hexahydrosiladefenidol, and a pKB of 7.78 and 7.95 was calculated for the proximal and distal vagina, respectively. Inositol phosphate production was significantly increased in both regions of the vagina following 20-min exposure to 50 µM carbachol with higher levels detected in the proximal vagina compared with the distal (P < 0.05). Preliminary experiments indicated the presence of M2 and M3 receptors in the human vaginal muscularis as well as contraction of human vaginal muscularis to carbachol, indicating that our animal studies are relevant to human tissue. Our results provide strong evidence for the functional significance of M3 receptor expression in the vaginal muscularis.

vagina; smooth muscle; muscarinic receptor; female sexual response


Address for reprint requests and other correspondence: S. Chacko, Basic Urology Research Laboratory, Glenolden Research Bldg., 500 S. Ridgeway Ave., Glenolden, PA 19036-2307 (e-mail: chackosk{at}mail.med.upenn.edu).






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