Clonidine inhibits the isoproterenol-induced desensitization of the beta noradrenergic activated adenylate cyclase system in astrocytes.

Studies were conducted to determine if alpha agonists could influence the desensitization of the beta-noradrenergic receptor activated adenylate cyclase system. Pretreatment of astrocyte cultures with isoproterenol results in a rapid decrease in the cyclic AMP response to subsequent re-exposure to this agonist. The cyclic AMP response to isoproterenol in astrocytes pre-exposed for 2 h to isoproterenol plus clonidine was 2-3 times higher than in cells pre-exposed to isoproterenol alone. The response in astrocytes pretreated with phenylephrine plus isoproterenol was not different from that in cells pretreated with isoproterenol alone. Cyclic AMP may be involved in the effects elicited by clonidine, since this agonist can inhibit the accumulation of cyclic AMP in these cells. Also pretreatment with isobutylmethylxanthine decreases the cyclic AMP response to isoproterenol. The results suggest that clonidine can effect the desensitization of the noradrenergic receptor coupled adenylate cyclase system independent of effects on neurotransmitter release.