Chloroethylclonidine irreversibly activates postjunctional alpha 2-adrenoceptors in the dog saphenous vein.
This study was aimed at analysing the contractile response of the dog saphenous vein to chloroethylclonidine. At 37 degrees C, chloroethylclonidine (0.1-100 mumol.l-1) caused a long-lasting contraction in both proximal and distal segments of the dog saphenous vein, reaching 77.6 and 52.6% of the maximal response to phenylephrine, respectively. At 18 degrees C, and in both segments, the maximal response to chloroethylclonidine was markedly reduced, whereas that to phenylephrine was not changed and that to UK-14,304 was enhanced. The response to chloroethylclonidine was unaffected by pretreatment with cocaine. Warming to 37 degrees C caused contraction of strips which at 18 degrees C had remained unresponsive to chloroethylclonidine, even if these strips were repeatedly washed before warming. At 18 degrees C, chloroethylclonidine (100 mumol.l-1) did not alter the responses to UK-14,304 and phenylephrine. At 37 degrees C, the contractile response to chloroethylclonidine was antagonized by yohimbine, rauwolscine and prazosin, with the potency rank yohimbine = rauwolscine > prazosin. Phenoxybenzamine (30 nmol.l-1) displaced the concentration-response curve to chloroethylclonidine to the right and depressed its maximum. After phenoxybenzamine, yohimbine continued to be more effective than prazosin, which remained very potent.(ABSTRACT TRUNCATED AT 250 WORDS)
Nunes
J P
JP
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Guimarães
S
S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000477:Alkylating Agents; D011810:Quinoxalines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; C051731:chlorethylclonidine; D000068438:Brimonidine Tartrate; D003042:Cocaine; D003000:Clonidine