title: Evidence of cyclic AMP-independent action of glucagon on calcium mobilization in rat hepatocytes.
abstract: Glucagon increases the cytoplasmic free calcium concentration as measured by aequorin bioluminescence. It has been proposed by Wakelam et al. (Nature 323 (1986) 68-71) that low concentrations of glucagon mobilize calcium from an intracellular pool by causing polyphosphoinositide breakdown. To identify whether cyclic AMP mediates changes in the cytoplasmic free calcium concentration ([Ca2+]c) induced by glucagon, the effects of forskolin and exogenous cyclic AMP on [Ca2+]c were compared with that of glucagon in aequorin-loaded hepatocytes. Although the magnitudes of the [Ca2+]c responses to 250 microM forskolin and 1 mM 8-bromo cyclic AMP were identical to that of 5 nM glucagon, these two agents induced a more prolonged elevation of [Ca2+]c. Glucagon-induced elevation of [Ca2+]c was accompanied by a smaller increase in cyclic AMP than that induced by forskolin. When the cyclic AMP response to glucagon was potentiated by an inhibitor of phosphodiesterase, 3-isobutyl-1-methylxanthine, the glucagon-induced increase in [Ca2+]c was not affected. Conversely, when the cyclic AMP response to glucagon was reduced by pretreatment of the cells with angiotensin II, glucagon-induced changes in [Ca2+]c were rather enhanced. Furthermore, vasopressin potentiated glucagon-induced changes in [Ca2+]c despite the reduction of the cyclic AMP response to glucagon. In the presence of 1 microM extracellular calcium, angiotensin II did not enhance glucagon-induced changes in [Ca2+]c. These results suggest that at least part of the action of 5 nM glucagon on calcium mobilization is independent of cyclic AMP.
authors: Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
authors: T
authors: T
authors: Mine
authors: I
authors: I
authors: Kojima
authors: E
authors: E
authors: Ogata
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000331:Aequorin; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000096:biosynthesis / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D005934:Glucagon / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D014667:Vasopressins; D000804:Angiotensin II; D005576:Colforsin; D000331:Aequorin; D005934:Glucagon; D000242:Cyclic AMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine