Calmodulin plays a dominant role in determining neurotransmitter regulation of neuronal adenylate cyclase.
Ca2+, through the mediation of calmodulin, stimulates the activity of brain adenylate cyclase. The growing awareness that fluctuating Ca2+ concentrations play a major role in intracellular signalling prompted the present study, which aimed to investigate the implications for neurotransmitter (receptor) regulation of enzymatic activity of this calmodulin regulation. The role of Ca2+/calmodulin in regulating neurotransmitter-mediated inhibition and stimulation was assessed in a number of rat brain areas. Ca2+/calmodulin stimulated adenylate cyclase activity in EGTA-washed plasma preparations from each region studied--from 1.3-fold (in striatum) to 3.4-fold (in cerebral cortex). The fold-stimulation produced by Ca2+/calmodulin was decreased in the presence of GTP, forskolin, or Mn2+. In EGTA-washed membranes, receptor-mediated inhibition of adenylate cyclase was strictly dependent upon Ca2+/calmodulin stimulation in all regions, except striatum. A requirement for Mg2+ in combination with Ca2+/calmodulin to observe neurotransmitter-mediated inhibition was also observed. In contrast, receptor-mediated stimulation of activity was much greater in the absence of Ca2+/calmodulin. The findings demonstrate that ambient Ca2+ concentrations, in concert with endogenous calmodulin, may play a central role in dictating whether inhibition or stimulation of adenylate cyclase by neurotransmitters may proceed.
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008345:Manganese / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D051381:Rats
D002147:Calmodulin; D018377:Neurotransmitter Agents; D005576:Colforsin; D008345:Manganese; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D002118:Calcium