Calmodulin may play a pivotal role in neurotransmitter-mediated inhibition and stimulation of rat cerebellar adenylate cyclase.
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.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002147:Calmodulin / Q000494:pharmacology / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D002531:Cerebellum / Q000201:enzymology*; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D018377:Neurotransmitter Agents / Q000502:physiology*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats
D002147:Calmodulin; D018377:Neurotransmitter Agents; D010660:Phenylisopropyladenosine; D004533:Egtazic Acid; D000262:Adenylyl Cyclases; D002118:Calcium