COMPARISON OF ALPHA(1A)-ADRENOCEPTOR AND ALPHA(1B)-ADRENOCEPTOR COUPLING TO INOSITOL PHOSPHATE FORMATION IN RAT-KIDNEY

We have compared the coupling mechanisms of rat renal alpha(1A)- and a lpha(1B)-like adrenoceptors to inositol phosphate formation. The exper iments were performed in parallel in native renal tissue preparations and in those where alpha(1B)-adrenoceptors had been inactivated by tre atment with 10 mu mol/l chloroethylclonidine for 30 min at 37 degrees C; renal slices were used in most experiments but isolated renal cells were also used in some cases. The Ca2+ chelating agent, EGTA (5 mmol/ l), reduced noradrenaline-stimulated inositol phosphate formation in n ative but enhanced it in chloroethylclonidine-treated renal slices. Th e inhibitory effect of EGTA was not mimicked by 100 nmol/l nifedipine. Inactivation of 87% of cellular Gi by 16-20 h treatment with 500 ng/m l pertussis toxin did not significantly affect noradrenaline-stimulate d inositol phosphate formation in isolated renal cells but abolished t he inhibitory effect of chloroethylclonidine. The adenylate cyclase ac tivator, forskolin (20 mu mol/l), inhibited noradrenaline-stimulated i nositol phosphate formation in native and chloroethylclonidine-treated slices, and the inhibitory effects of chloroethylclonidine treatment and forskolin were additive. We conclude that in rat kidney inositol p hosphate formation via alpha(1B)-like adrenoceptors may involve the in flux of extracellular Ca2+ and a pertussis toxin-sensitive G-protein b ut is insensitive to inhibition by forskolin. In contrast alpha(1A)-li ke adrenoceptor-mediated inositol phosphate formation does not require the presence of extracellular Ca2+ or of G(i) and is sensitive to inh ibition by forskolin. In comparison to published data from other model systems we further conclude that the signaling mechanisms of alpha(1) -adrenoceptor subtypes may depend on their cellular environment.