(-)-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.
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)
Martin
P L
PL
Department of Pharmacology, Whitby Research, Inc., Richmond, Virginia.
Kelly
M
M
Cusack
N J
NJ
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*
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