RT Journal Article SR Electronic T1 Calmodulin may play a pivotal role in neurotransmitter-mediated inhibition and stimulation of rat cerebellar adenylate cyclase. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 127 OP 132 VO 32 IS 1 A1 M K Ahlijanian A1 D M Cooper YR 1987 UL http://molpharm.aspetjournals.org/content/32/1/127.abstract AB Adenylate cyclase activity was stimulated 2.5-fold by exogenous Ca2+/calmodulin (CaM) (1 microM) in rat cerebellar plasma membranes which had been depleted of endogenous Ca2+/CaM. In EGTA-washed membranes, phenylisopropyladenosine (an adenosine receptor agonist) was unable to inhibit adenylate cyclase activity unless exogenous Ca2+/CaM was included in the assay. Conversely, isoproterenol (a beta-adrenergic receptor agonist) was able to stimulate adenylate cyclase activity only in the absence of Ca2+/CaM. The regulation of adenylate cyclase activity by guanyl-5'-yl-imidodiphosphate [Gpp(NH)p, a nonhydrolyzable guanine nucleotide analog, used to monitor interactions between guanine nucleotide-binding proteins and the catalytic unit of adenylate cyclase] was similar to that of phenylisopropyladenosine and isoproterenol; i.e., Gpp(NH)p produced inhibition exclusively in the presence of Ca2+/CaM, whereas only stimulation was observed in the absence of Ca2+/CaM. These results suggest that changes in intracellular Ca2+ concentrations may determine whether adenylate cyclase can be stimulated or inhibited by neurotransmitters.