Activation of β-adrenergic receptors during sexual arousal facilitates vaginal lubrication by regulating vaginal epithelial Cl(-) secretion.
BACKGROUND
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 β-AR in sexual arousal, however, has not yet been investigated.


OBJECTIVE
The 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.


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 (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.


METHODS
Changes of ISC responses; mRNA, protein expressions and localization of β-AR; [cAMP]i ; vaginal lubrication.


RESULTS
Serosal 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.


CONCLUSIONS
Activation 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.
School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
Qing
Q
Sun
Jiehong
J
Huang
Deng-Liang
DL
Yang
Xiao-Nian
XN
Cao
Wen-Liang
WL
Zhou
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000502:physiology*; D001565:Benzoates / Q000494:pharmacology; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D053778:Thiazolidines / Q000494:pharmacology; D014621:Vagina / Q000378:metabolism*
C482900:3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone; D000317:Adrenergic alpha-Antagonists; D001565:Benzoates; D002712:Chlorides; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D053778:Thiazolidines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011433:Propranolol; D000242:Cyclic AMP
Cl−; Lubrication; Rat; Sexual Arousal; Short Circuit Current; VK2/E6E7; Vagina; Vaginal Epithelium; β-Adrenergic Receptors