CHLOROETHYLCLONIDINE IS A PARTIAL ALPHA(1A)-ADRENOCEPTOR AGONIST IN CELLS EXPRESSING RECOMBINANT ALPHA(1)-ADRENOCEPTOR SUBTYPES

Chloroethylclonidine increased cytosol [Ca2+] in rat-1 fibroblasts sta bly expressing alpha(1a)- adrenoceptors. The effect of the imidazoline was dose-dependent with a maximal effect (approximate to 3-fold incre ase 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)-adre noceptors. Noradrenaline (1 mu M) induced a much bigger effect (approx imate to 6-8-fold) in the same cells. When chloroethylclonidine was ad ded before noradrenaline a dose-dependent inhibition of the effect of the natural catecholamine was observed. Chloroethylclonidine did not m odified cytosol [Ca2+] in rat-1 fibroblast expressing alpha(1b)- or al pha(1d)-adrenoceptors. However, the imidazoline acutely inhibited the effect of noradrenaline in these cells. It is concluded that chloroeth ylclonidine interacts with alpha(1a)-adrenoceptors as a partial agonis t inducing Ca2+ mobilization in st very short time frame and that it i s able to inhibit the action of noradrenaline when co-incubated with t he catecholamine in cells expressing any of the three alpha(1)-adrenoc eptor subtypes. (C) 1997 Elsevier Science Inc.