Chloroethylclonidine is a partial alpha(1A)-adrenoceptor agonist in cells expressing recombinant alpha(1)-adrenoceptor subtypes

Chloroethylclonidine increased cytosol [Ca2+] in rat-1 fibroblasts stably expressing alpha(1a)- adrenoceptors. The effect of the imidazoline was dose-dependent with a maximal effect (approximate to 3-fold increase in [Ca2+](i)) at 10 mu M and it was blocked by phentolamine and 5-methyl urapidil, indicating that it was mediated through alpha(1)-adrenoceptors. Noradrenaline (1 mu M) induced a much bigger effect (approximate to 6-8-fold) in the same cells. When chloroethylclonidine was added before noradrenaline a dose-dependent inhibition of the effect of the natural catecholamine was observed. Chloroethylclonidine did not modified cytosol [Ca2+] in rat-1 fibroblast expressing alpha(1b)- or alpha(1d)-adrenoceptors. However, the imidazoline acutely inhibited the effect of noradrenaline in these cells. It is concluded that chloroethylclonidine interacts with alpha(1a)-adrenoceptors as a partial agonist inducing Ca2+ mobilization in st very short time frame and that it is able to inhibit the action of noradrenaline when co-incubated with the catecholamine in cells expressing any of the three alpha(1)-adrenoceptor subtypes. (C) 1997 Elsevier Science Inc.