TY - JOUR
T1 - Calmodulin stimulation and calcium regulation of smooth muscle adenylate cyclase activity
AU - Piascik, M. T.
AU - Babich, M.
AU - Rush, M. E.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1983
Y1 - 1983
N2 - The Ca2+-dependent regulation of the adenylate cyclase activity associated with microsomes isolated from bovine aortic smooth muscle has been studied. Calmodulin content of microsomal membranes employed in these studies was 80 ± 14 ng/mg as determined by specific radioimmunoassay. In the absence of exogenous calmodulin, Ca2+ concentrations greater than 0.8 μM inhibited adenylate cyclase activity with one-half-maximal inhibition occurring at 2.5 μM Ca2+. In the presence of 5 or 9 μM bovine testis calmodulin, Ca2+ stimulated smooth muscle adenylate cyclase activity with one-half-maximal stimulation occurring at 0.2 μM for both 5 and 9 μM calmodulin. Calmodulin stimulation was observed between 0.1 and 0.8 μM Ca2+. Despite the presence of calmodulin, Ca2+ concentrations greater than 0.8 μM were inhibitory to smooth muscle adenylate cyclase activity. However, calmodulin reduced the sensitivity of the enzyme to inhibition by Ca2+. Trifluoperazine (100 μM) reversed both the calmodulin-dependent-stimulation of cyclase activity and the calmodulin-induced decrease in sensitivity to the inhibitory actions of Ca2+. Trifluoperazine alone shifted the curve describing Ca2+ inhibition of cyclase activity to the left. The value of Ca2+ for one-half-maximal inhibition decreased from 2.9 to 1.2 μM. The trifluoperazine-induced shift was reversed by exogenous calmodulin. These data suggest: 1) Ca2+, at physiological concentrations, can stimulate as well as inhibit smooth muscle adenylate cyclase activity; 2) the stimulation of adenylate cyclase activity is medidated by calmodulin; 3) the Ca2+-calmodulin complex reduces the sensitivity of smooth muscle adenylate cyclase to the inhibitory actions of Ca2+; and 4) the level of calmodulin associated with smooth muscle adenylate cyclase may modulate the response (both stimulatory and inhibitory) of the enzyme to Ca2+.
AB - The Ca2+-dependent regulation of the adenylate cyclase activity associated with microsomes isolated from bovine aortic smooth muscle has been studied. Calmodulin content of microsomal membranes employed in these studies was 80 ± 14 ng/mg as determined by specific radioimmunoassay. In the absence of exogenous calmodulin, Ca2+ concentrations greater than 0.8 μM inhibited adenylate cyclase activity with one-half-maximal inhibition occurring at 2.5 μM Ca2+. In the presence of 5 or 9 μM bovine testis calmodulin, Ca2+ stimulated smooth muscle adenylate cyclase activity with one-half-maximal stimulation occurring at 0.2 μM for both 5 and 9 μM calmodulin. Calmodulin stimulation was observed between 0.1 and 0.8 μM Ca2+. Despite the presence of calmodulin, Ca2+ concentrations greater than 0.8 μM were inhibitory to smooth muscle adenylate cyclase activity. However, calmodulin reduced the sensitivity of the enzyme to inhibition by Ca2+. Trifluoperazine (100 μM) reversed both the calmodulin-dependent-stimulation of cyclase activity and the calmodulin-induced decrease in sensitivity to the inhibitory actions of Ca2+. Trifluoperazine alone shifted the curve describing Ca2+ inhibition of cyclase activity to the left. The value of Ca2+ for one-half-maximal inhibition decreased from 2.9 to 1.2 μM. The trifluoperazine-induced shift was reversed by exogenous calmodulin. These data suggest: 1) Ca2+, at physiological concentrations, can stimulate as well as inhibit smooth muscle adenylate cyclase activity; 2) the stimulation of adenylate cyclase activity is medidated by calmodulin; 3) the Ca2+-calmodulin complex reduces the sensitivity of smooth muscle adenylate cyclase to the inhibitory actions of Ca2+; and 4) the level of calmodulin associated with smooth muscle adenylate cyclase may modulate the response (both stimulatory and inhibitory) of the enzyme to Ca2+.
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M3 - Article
C2 - 6885807
AN - SCOPUS:0020590733
SN - 0021-9258
VL - 258
SP - 10913
EP - 10918
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 18
ER -