title: Vasopressin-induced mouse urethral contraction is modulated by caveolin-1.
abstract: Caveolae are 50-100nm large invaginations in the cell membrane that are considered to play roles in receptor signaling. Here we aimed to investigate the expression and distribution of the arginine-vasopressin (AVP) V1a receptor and its functional dependence on caveolin-1 (Cav1) in the mouse urethra. Female Cav1 knockout (KO) and wild type (WT) mice were used, and urethral preparations were micro-dissected for mechanical experiments. Methyl-β-cyclodextrin (mβcd) was used to deplete cholesterol and to disrupt caveolae. Protein expression and localization was determined using immunofluorescence and western blotting and transcript expression was determined by qRT-PCR. We found that Cav1 and AVP V1a receptors were expressed in urethral smooth muscle cells with apparent co-localization at the cell membrane. AVP caused urethral contraction that was inhibited by the V1a receptor antagonist SR49059. Concentration-response curves for AVP were right-shifted and maximal contraction was reduced in Cav1 KO mice and after mβcd treatment. In addition to caveolin-1 we also detected caveolin-2, cavin-1 and cavin-3 in the mouse urethra by western blotting. Caveolin-2, cavin-1 and cavin-3 as well as V1a receptor expression was reduced in KO urethra. We conclude that AVP regulates urethral contractility via the V1a receptor through a Cav1-dependent mechanism involving, in part, altered V1a receptor expression.
authors: Department of Experimental Medical Science, BMC D12, Lund University, SE-221 84 Lund, Sweden; Department of Urology, Qing Yuan City People׳s Hospital, Jinan University, Guang Dong, China.
authors: Jianwen
authors: J
authors: Zeng
authors: Department of Experimental Medical Science, BMC D12, Lund University, SE-221 84 Lund, Sweden.
authors: Mari
authors: M
authors: Ekman
authors: Department of Experimental Medical Science, BMC D12, Lund University, SE-221 84 Lund, Sweden.
authors: Mario
authors: M
authors: Grossi
authors: Department of Experimental Medical Science, BMC D12, Lund University, SE-221 84 Lund, Sweden.
authors: Daniel
authors: D
authors: Svensson
authors: Department of Experimental Medical Science, BMC D12, Lund University, SE-221 84 Lund, Sweden.
authors: Bengt-Olof
authors: BO
authors: Nilsson
authors: Department of Urology, Qing Yuan City People׳s Hospital, Jinan University, Guang Dong, China.
authors: Chonghe
authors: C
authors: Jiang
authors: Department of Urology, Clinical Sciences, Lund University, Lund, Sweden.
authors: Bengt
authors: B
authors: Uvelius
authors: Department of Experimental Medical Science, BMC D12, Lund University, SE-221 84 Lund, Sweden. Electronic address: karl.sward@med.lu.se.
authors: Karl
authors: K
authors: Swärd
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000172:deficiency; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D017483:Receptors, Vasopressin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014521:Urethra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D051242:Caveolin 1; D017483:Receptors, Vasopressin; D014667:Vasopressins; D002784:Cholesterol
keywords: Arginine-vasopressin (AVP); Caveolin-1; Caveolin-1 knockout; Methyl-β-cyclodextrin; Urethra; V(1a) receptor