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

Abstract

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 M(2) and M(3) 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 M(3) antagonist para-fluoro-hexahydrosiladefenidol, and a pK(B) 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 muM carbachol with higher levels detected in the proximal vagina compared with the distal (P < 0.05). Preliminary experiments indicated the presence of M(2) and M(3) 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 M(3) receptor expression in the vaginal muscularis.

Simulated vaginal delivery causes transients vaginal smooth muscle hypersensitivity and urethral sphincter dysfunction

“…This observation may contribute to the hypersensitivity described above. The M2 and M3 receptors have been previously demonstrated in vaginal tissue and muscarinic activation induces contraction, although their physiologic role remains unknown 14,23 . The upregulation of M2 we demonstrate at 3 days, might therefore further explain the earlier described hypersensitivity.…”

Morphological and Functional Changes in the Vagina following Critical Lifespan Events in the Ewe

“…Contractility of female vaginal tissue has been reported in few studies using various agents that can make smooth muscles contract (i.e., KCl, carbachol, phenylephrine, others) [43][44][45]. However, all specimens have been obtained from elder gynecological patients (hysterectomy for benign lesions or malignancy, POP) and no comparison between comparable time points during life has been performed so far.…”

Regional Differences in Rat Vaginal Smooth Muscle Contractility and Morphology

“…To evaluate muscle-mediated contractions, contractile response to increasing concentrations of KCl (10,20,30,40,60,80, and 120 mmol/L) was measured (n ¼ 7). These concentrations were chosen based on the results from dose-response curves in preliminary experiments, in which we found the greatest change in force between 10 and 40 mmol/L KCl, with a plateau generally reached by 120 mmol/L KCl.…”

“…Regional differences have been demonstrated in both the rabbit and the rat. [8][9][10] Histologically, a greater percentage of smooth muscle is found in the proximal vagina, compared to the distal region. 8,9 Variation in contractile patterns has been observed with a phasic contractile response predominantly observed in the proximal vagina and a tonic response seen in the distal vagina.…”