title: Alpha(1D)-adrenoceptors mediate nerve and agonist-evoked contractions in mouse vas deferens: evidence obtained from knockout technology.
abstract: 1 It has been demonstrated that nerve-evoked contractions of the rat vas deferens involve alpha(1D)-adrenoceptors. Definitive evidence for a similar alpha(1D)-adrenoceptor-mediated response in mouse vas deferens has been more difficult to obtain. In this study, we have used alpha(1D)-adrenoceptor knockout (alpha(1D)-KO) mice to aid in the pharmacological characterization. 2 Mouse whole vas deferens was stimulated with a single pulse every 5 min. Once a stable response had been obtained, vehicle or antagonist was administered cumulatively at 5-min intervals and a response to stimulation obtained 5 min later. Cumulative concentration-response curves were also obtained for noradrenaline. 3 In vas deferens from alpha(1D)-KO mice, the contractile response to low concentrations of noradrenaline and the contractile response to a single stimulus were significantly reduced as compared to wild type (WT). 4 The alpha(1D)-adrenoceptor selective antagonist, BMY 7378, produced a concentration-dependent inhibition of single pulse-evoked contractions of vas deferens from WT and alpha(1D)-KO mice. BMY 7378 was significantly less potent in inhibiting stimulation-evoked contractions in vas deferens from alpha(1D)-KO mice. 5 It is concluded that alpha(1D)-adrenoceptors mediate a component of nerve- and agonist-evoked contractions of the vas deferens of WT mice.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Bexis
authors.forename: L
authors.initials: L
authors.lastname: Cleary
authors.forename: J C
authors.initials: JC
authors.lastname: McGrath
authors.forename: A
authors.initials: A
authors.lastname: Tanoue
authors.forename: G
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: J R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C547720:Adra1d protein, mouse; C547721:Adra1d protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D003042:Cocaine; C053428:BMY 7378; D009638:Norepinephrine