title: How important is the α1-adrenoceptor in primate and rodent proximal urethra? Sex differences in the contribution of α1-adrenoceptor to urethral contractility.
abstract: Urethral smooth muscle (USM) contributes to urinary continence by contracting during the urine storage phase, which is mainly mediated by activation of postjunctional α1-adrenoceptors. Males and females show differences in the functioning of the lower urinary tract and the most common urinary tract symptoms (LUTS). LUTS in men typically occur in association with bladder outlet obstruction, whereas in women urinary urge-incontinence symptoms are more common. Therefore, this study aimed to evaluate sex differences in α1-adrenoceptor subtype expression and their importance in proximal urethra contraction in the mouse (C57BL6/J) and marmoset (Callithrix jacchus). Contractile responses to phenylephrine, norepinephrine, potassium chloride (KCl), and electrical-field stimulation (EFS) were evaluated. Phenylephrine, norepinephrine, KCl, and EFS produced markedly greater contractions in male mice and marmoset USM compared with females. The sex differences remained unchanged byNω-nitro-l-arginine (l-NAME; nitric oxide synthase inhibitor), atropine (muscarinic receptor antagonist), and PPADS (P2X1-purinoceptor antagonist). Additionally, selective α1A(but not α1B- and α1D-)-adrenoceptor antagonists significantly reduced phenylephrine-induced USM contractions. qRT-PCR for α1A-,B-, andD-adrenoceptor subtypes revealed a marked presence of the α1A-adrenoceptor subtype in male USM, but not females. Male mouse urethra also exhibited a higher tyrosine hydroxylase mRNA expression. Histomorphometric analysis showed a greater USM area in male than female mice. In conclusion, male mouse and marmoset proximal USM shows strong α1A- adrenoceptor-induced contractions and abundant α1A-adrenoceptor expression, whereas α1A-adrenoceptor-mediated mechanisms are much less important in females. The differential expression of α1-adrenoceptors in the proximal urethra may contribute to the higher incidence of urinary incontinence in women and obstructed voiding in men.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; edu86alex@gmail.com.
authors.forename: Eduardo C
authors.identifier: 0000-0002-9482-6799
authors.initials: EC
authors.lastname: Alexandre
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: de Oliveira
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Campos
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Kiguti
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Fabiano B
authors.initials: FB
authors.lastname: Calmasini
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Fábio H
authors.initials: FH
authors.lastname: Silva
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom; and.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Grant
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Edson
authors.identifier: 0000-0003-2201-8247
authors.initials: E
authors.lastname: Antunes
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014521:Urethra / Q000187:drug effects / Q000378:metabolism*
chemical_list: C547714:Adra1a protein, mouse; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D014446:Tyrosine 3-Monooxygenase
keywords: EFS; incontinence; norepinephrine; phenylephrine; tyrosine hydroxylase