title: (-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0923), a selective D2 dopamine receptor agonist demonstrates the presence of D2 dopamine receptors in the mouse vas deferens but not in the rat vas deferens.
abstract: Experiments were carried out using the D2 dopamine receptor-selective agonist (-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0923) in the rat and the mouse isolated vas deferens to determine whether these tissues contained inhibitory D2 receptors in addition to their inhibitory alpha-2 adrenoceptors. In the mouse vas deferens N-0923 and the alpha-2 adrenoceptor agonist clonidine inhibited the electrically evoked twitch responses. The actions of clonidine, but not of N-0923, were antagonized by the alpha-2 antagonist idazoxan (pKb = 7.9), and responses to N-0923 were antagonized by the D2 antagonist sulpiride (pKb = 8.1). In the rat vas deferens, clonidine, but not N-0923, inhibited the twitch responses and these inhibitions were antagonized by idazoxan (pKb = 7.9) but not by sulpiride. Other D2 receptor agonists were tested in the mouse and in the rat vas deferens for their ability to activate D2 and alpha-2 receptors, respectively. At the D2 receptors in the mouse vas deferens (alpha-2 blocked) the potency order was (+)-propyl-9-hydroxy-naphtoxazine > pergolide > N-0923 = apomorphine > bromocriptine > quinpirole > dopamine. At the alpha-2 receptors in the rat vas deferens the potency order was pergolide > bromocriptine > (+)-propyl-9-hydroxynapthoxazine > apomorphine > quinpirole > or = dopamine. N-0923 was inactive but antagonized the responses to clonidine. N-0923 was therefore the most D2 receptor selective agonist tested.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Whitby Research, Inc., Richmond, Virginia.
authors.forename: P L
authors.initials: PL
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Kelly
authors.forename: N J
authors.initials: NJ
authors.lastname: Cusack
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D015259:Dopamine Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019329:Idazoxan; D008297:Male; D051379:Mice; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects / Q000648:ultrastructure*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D013469:Sulpiride; C047508:rotigotine; D003000:Clonidine; D019329:Idazoxan