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

IntroductionVaginal 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 β‐AR in sexual arousal, however, has not yet been investigated.AimThe goal of this study was to reveal the functional role of β‐AR in modulating vaginal lubrication during sexual arousal and the mechanisms underlying the process.MethodsThe 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 (ISC) of rat vaginas incubated in vitro, enzyme‐linked immunosorbent assay (ELISA), and measurement of vaginal lubrication in vivo, respectively. The expressions of β‐AR in vaginal epithelium were analyzed by reverse transcription‐polymerase chain reaction, western blot, and immunofluorescence.Main Outcome MeasuresChanges of ISC responses; mRNA, protein expressions and localization of β‐AR; [cAMP]i; vaginal lubrication.ResultsSerosal application of adrenaline induced an increase of ISC across rat vaginal epithelium that blocked by propranolol, a β‐AR antagonist, rather than phentolamine, an α‐AR antagonist. β1/2‐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.ConclusionsActivation of epithelial β‐AR facilitates vaginal lubrication during sexual arousal by stimulating vaginal epithelial Cl− secretion in a cAMP‐dependent pathway. Thus, vaginal epithelial β‐AR might be another regulator of vaginal sexual arousal responses. Sun Q, Huang J, Yang D‐L, Cao X‐N, and Zhou W‐L. Activation of β‐adrenergic receptors during sexual arousal facilitates vaginal lubrication by regulating vaginal epithelial Cl− secretion. J Sex Med 2014;11:1936–1948.