โ Scribed by Dermot M. F. Cooper; Michael K. Ahlijanian; Edward Perez-Reyes
No coin nor oath required. For personal study only.
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. Ca*+/calmodulin stimulated adenylate cyclase activity in EGTA-washed plasma preparations from each region studied-from 1 .%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 Ca*+/calmodulin stimulation in all regions, except striatum. A requirement for Mg2+ in combination with Ca*+/calmodulin to observe neurotransmitter-mediated inhibition was also observed. In contrast, receptormediated stimulation of activity was much greater in the absence of Ca2+/ calmodulin. The findings demonstrate that ambient Ca*' concentrations, in concert with endogenous calmodulin, may play a central role in dictating whether inhibition or stimulation of adenylate cyclase by neurotransmitters may proceed.
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