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Calmodulin plays a dominant role in determining neurotransmitter regulation of neuronal adenylate cyclase
Author(s) -
Cooper Dermot M. F.,
Ahlijanian Michael K.,
PerezReyes Edward
Publication year - 1988
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240360410
Subject(s) - calmodulin , egta , adenylate kinase , cyclase , stimulation , neurotransmitter , forskolin , biology , receptor , medicine , endocrinology , chemistry , biochemistry , calcium , enzyme
Ca 2+ , through the mediation of calmodulin, stimulates the activity of brain adenylate cyclase. The growing awareness that fluctuating Ca 2+ , 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 Ca 2+ /calmodulin in regulating neurotransmitter‐mediated inhibition and stimulation was assessed in a number of rat brain areas. Ca 2+ /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 Ca 2+ /calmodulin was decreased in the presence of GTP, forskolin, or Mn 2+ . In EGTA‐washed membranes, receptor‐mediated inhibition of adenylate cyclase was strictly dependent upon Ca 2+ /calmodulin stimulation in all regions, except striatum. A requirement for Mg 2+ in combination with Ca 2+ /calmodulin to observe neurotransmitter‐mediated inhibition was also observed. In contrast, receptor‐mediated stimulation of activity was much greater in the absence of Ca 2+ /calmodulin. The findings demonstrate that ambient Ca 2+ concentrations, in concert with endogenous calmodulin, may play a central role in dictating whether inhibition or stimulation of adenylate cyclase by neurotransmitters may proceed.