Conflicting opinions were recently expressed concerning the possible effect of α2-adrenergic agonists upon cyclic AMP production in pancreatic islets. In the present: study, clonidine inhibited glucose-induced insulin release from rat pancreatic islets, this inhibitory effect being abolished by idazoxan. Clonidine did not suppress the capacity of forskolin to augment glucose-induced insulin release. In a particulate subcellular fraction derived from the islets, adenylate cyclase was activated by calmodulin (in the presence of Ca2+), NaF, GTP, L-arginine, and forskolin, and slightly inhibited by clonidine. The inhibitory action of clonidine upon basal adenylate cyclase activity was more pronounced in islet crude homogenates. The inhibitory effect of clonidine was antagonized by forskolin whether in the particulate fraction or crude homogenate. At variance with the modest effects of glucagon, D-glucose, L-arginine, or a tumor-promoting phorbol ester upon cyclic AMP production by intact islets, forskolin caused a six-fold increase in cyclic AMP production. Clonidine inhibited cyclic AMP production by intact islets, whether in the absence or presence of forskolin. It is proposed that the inhibitory action of clonidine upon insulin release is attributable, in part at least, to inhibition of adenylate cyclase.
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June 01 1984
Inhibitory effect of clonidine upon adenylate cyclase activity, cyclic AMP production, and insulin release in rat pancreatic islets
P. Garcia-Morales;
P. Garcia-Morales
1Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Laboratory of Experimental Medicine, Brussels Free University School of Medicine, Brussels, Belgium
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S. P. Dufrane;
S. P. Dufrane
1Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Laboratory of Experimental Medicine, Brussels Free University School of Medicine, Brussels, Belgium
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A. Sener;
A. Sener
1Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Laboratory of Experimental Medicine, Brussels Free University School of Medicine, Brussels, Belgium
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I. Valverde;
I. Valverde
1Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Laboratory of Experimental Medicine, Brussels Free University School of Medicine, Brussels, Belgium
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W. J. Malaisse
W. J. Malaisse
1Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Laboratory of Experimental Medicine, Brussels Free University School of Medicine, Brussels, Belgium
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Publisher: Portland Press Ltd
Received:
June 06 1984
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 1984 The Biochemical Society
1984
Biosci Rep (1984) 4 (6): 511–521.
Article history
Received:
June 06 1984
Citation
P. Garcia-Morales, S. P. Dufrane, A. Sener, I. Valverde, W. J. Malaisse; Inhibitory effect of clonidine upon adenylate cyclase activity, cyclic AMP production, and insulin release in rat pancreatic islets. Biosci Rep 1 June 1984; 4 (6): 511–521. doi: https://doi.org/10.1007/BF01122227
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