CHRONIC ELEVATION OF CAMP LEVELS INDUCES CHANGES IN THE ADENYLATE-CYCLASE SYSTEM, OPIATE RECEPTOR SENSITIVITY AND LEVELS OF GS-MESSENGER-RNA IN CULTURED NEURONS

Neurons in primary culture were treated (5 days) with the adenylate cyclase stimulator 10(-5) M forskolin. The basal adenylate cyclase was decreased by 57%. The acute stimulatory effect of forskolin was down-regulated by 48%. The inhibitory effects of the 3 opiate receptor agonists (mu, delta and kappa) were partly abolished. The abundance of mRNA encoding the stimulatory G-protein (G(s)) was decreased prominently. The data indicate that the cAMP system in neuronal cells in primary culture is under dynamic regulation, possibly including altered G(s)-protein gene expression. Furthermore, long-term forskolin treatment might induce increased proliferation in susceptible neural blast cells.