Chloroethylclonidine irreversibly activates postjunctional alpha2-adrenoceptors in the dog saphenous vein

Open Access
Publisher Website
Google Scholar
Abstract
This study was aimed at analysing the contractile response of the dog saphenous vein to chloroethylclonidine. At 37°C, chloroethylclonidine (0.1–100 μmol·1−1) caused along-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°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°C caused contraction of strips which at 18°C had remained unresponsive to chloroethylclonidine, even if these strips were repeatedly washed before warming. At 18°C, chloroethylclonidine (100 μmol·1−1) did not alter the responses to UK-14,304 and phenylephrine. At 37°C, the contractile response to chloroethylclonidine was antagonized by yohimbine, rauwolscine and prazosin, with the potency rank yohimbine = rauwolscine > prazosin. Phenoxybenzamine (30 nmol · 1−1) 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. We concluded that: 1) the contractile response of the canine saphenous vein to chloroethylclonidine (both in the absence and in the presence of phenoxybenzamine) is predominantly alpha2-adrenoceptor-mediated since it is larger at the proximal than at the distal level of the vein and since it is more sensitive to yohimbine and rauwolscine than to prazosin; 2) the response to chloroethylclonidine and UK-14,304 are apparently due to activation of different alpha2-adrenoceptor subtypes, since prazosin was much more effective against chloroethylclonidine than against UK-14,304, and since at 18°C chloroethylclonidine “occupies” receptors without changing the response to UK-14,304; 3) there is a component of alphal-adrenoceptor stimulation in the response to chloroethylclonidine, since 30 nmol·1−1 phenoxybenzamine partly antagonized the effect of chloroethylclonidine; 4) since the responses to UK-14,304 and chloroethylclonidine are differently affected by cooling, there is some step (or steps) in the chain of events between the receptor and the final response, which is different in the two pathways.