Activation of β-Adrenergic Receptors During Sexual Arousal Facilitates Vaginal Lubrication by Regulating Vaginal Epithelial Cl- Secretion

Introduction. Vaginal lubrication, an indicator of sexual arousal and tissue health, increases significantly during genital sexual arousal. Adrenergic alpha-receptors (AR) are an important regulator of genital physiological responses involved in mediating vascular and nonvascular smooth muscle contractility; the role of beta-AR in sexual arousal, however, has not yet been investigated. Aim. The goal of this study was to reveal the functional role of beta-AR in modulating vaginal lubrication during sexual arousal and the mechanisms underlying the process. Methods. The effects of adrenaline on vaginal epithelial ion transport, intracellular cyclic adenosine monophosphate (cAMP) content ([cAMP](i)), and vaginal lubrication were investigated using short-circuit current (I-SC) of rat vaginas incubated in vitro, enzyme-linked immunosorbent assay (ELISA), and measurement of vaginal lubrication in vivo, respectively. The expressions of beta-AR in vaginal epithelium were analyzed by reverse transcription-polymerase chain reaction, western blot, and immunofluorescence. Main Outcome Measures. Changes of I-SC responses; mRNA, protein expressions and localization of beta-AR; [cAMP](i); vaginal lubrication. Results. Serosal application of adrenaline induced an increase of I-SC across rat vaginal epithelium that blocked by propranolol, a beta-AR antagonist, rather than phentolamine, an alpha-AR antagonist. beta 1/2-AR were both present in rat and human vaginal epithelial cells. Removing Cl- or application of CFTR(inh)-172, an inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR), abolished adrenaline-induced ISC responses. The elevated levels of [cAMP](i) induced by adrenaline were prevented by the pretreatment with propranolol. Vaginal lubrication measured in vivo showed that adrenaline or pelvic nerve stimulation caused a marked increase in vaginal lubrication, whereas pretreatment with propranolol or CFTR(inh)-172 reduced the effect. Conclusions. Activation of epithelial beta-AR facilitates vaginal lubrication during sexual arousal by stimulating vaginal epithelial Cl- secretion in a cAMP-dependent pathway. Thus, vaginal epithelial beta-AR might be another regulator of vaginal sexual arousal responses.