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, chloroethylcl onidine (0.1 - 100 mumol.l-1) caused a long-lasting contraction in bot h 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 chloroeth ylclonidine was markedly reduced, whereas that to phenylephrine was no t changed and that to UK-14,304 was enhanced. The response to chloroet hylclonidine was unaffected by pretreatment with cocaine. Warming to 3 7-degrees-C caused contraction of strips which at 18-degrees-C had rem ained unresponsive to chloroethylclonidine, even if these strips were repeatedly washed before warming. At 18-degrees-C, chloroethylclonidin e (100 mumol.l-1) did not alter the responses to UK-14,304 and phenyle phrine. At 37-degrees-C, the contractile response to chloroethylclonid ine was antagonized by yohimbine, rauwolscine and prazosin, with the p otency rank yohimbine = rauwolscine > prazosin. Phenoxybenzamine (30 n mol.l-1) displaced the concentration-response curve to chloroethylclon idine to the right and depressed its maximum. After phenoxybenzamine, yohimbine continued to be more effective than prazosin, which remained very potent. We concluded that: 1) the contractile response of the ca nine saphenous vein to chloroethylclonidine (both in the absence and i n the presence of phenoxybenzamine) is predominantly alpha2-adrenocept or-mediated since it is larger at the proximal than at the distal leve l of the vein and since it is more sensitive to yohimbine and rauwolsc ine than to prazosin; 2) the response to chloroethylclonidine and UK-1 4,304 are apparently due to activation of different alpha2-adrenocepto r subtypes, since prazosin was much more effective against chloroethyl clonidine than against UK-14,304, and since at 18-degrees-C chloroethy lclonidine ''occupies'' receptors without changing the response to UK- 14,304; 3) there is a component of alpha1-adrenoceptor stimulation in the response to chloroethylclonidine, since 30 nmol.l-1 phenoxybenzami ne partly antagonized the effect of chloroethylclonidine; 4) since the responses to UK-14,304 and chloroethylclonidine are differently affec ted by cooling, there is some step (or steps) in the chain of events b etween the receptor and the final response, which is different in the two pathways.