Using a1-adrenoceptor selective antagonists chlorethylclonidine (CEC) and WB4101, both functional and radioligand binding studies showed that rabbit aorta contains at least two pharmacologically distinct a1-adrenoceptor subtypes of approximately 10% ala and 90% alb receptors, and that each receptor subtype has a distinct role in the a1-adrenoceptor-mediated vasoconstrictive response through different biochemical mechanisms for increasing intracellular Ca2+; ala receptors cause tonic response predominantly dependent on the influx of extracellular Ca2 , while alb receptors stimulate phosphoinositides (PI) hydrolysis/intracellular Ca2+ mobilization and cause phasic response mainly independent of extracellular Ca2 . Incubation of rabbit aorta with 10 FM noradrenaline (NA) for 2 h resulted in a reduction in the phasic response and PI hydrolysis to NA with no change in the tonic response. Similar to the NA incubation, the protein kinase C stimulator PMA (1 FM) selectively attenuated aOb-receptor mediated PI hydrolysis and phasic contraction but had little effect on a la-receptor-mediated tonic response. The protein kinase C inhibitor H-7 (10 FM) blocked these inhibitory effects of PMA. Treatment with H-7 (10 FJM) prevented the NA-induced alb receptor desensitization in inositol monophosphate (IP) formation and phasic response. The results suggest that activation of C kinase may be involved in the development of selective desensitization of alb receptors by a short-time in vitro incubation of NA.
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