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A reassessment of the modulatory role of cyclic AMP in catecholamine secretion by chromaffin cells
Author(s) -
Parramón M.,
González M.P.,
OsetGasque M.J.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13257.x
Subject(s) - forskolin , medicine , endocrinology , adenosine , secretion , cyclic nucleotide , adenylate kinase , intracellular , cyclase , cyclic adenosine monophosphate , catecholamine , chemistry , calcium in biology , calcium , biology , receptor , stimulation , nucleotide , biochemistry , gene
1 The role of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) in the regulation of catecholamine (CA) secretion in chromaffin cells remains equivocal from previous studies. 2 In the present study the effect of this cyclic nucleotide on basal CA secretion, as well as on intracellular calcium and membrane potential has been examined. 3 Forskolin and the permeable cyclic AMP analogue, 8‐(4‐chlorphenylthio)‐adenosine‐3′‐5′ monophosphate cyclic (pClpcAMP), increased basal CA secretion in a dose‐dependent manner. The EC 50 S were 0.43 ± 0.10 μ m for forskolin and 39 ± 9 μ m for pClpcAMP. Other agonists with adenylate cyclase activity such as stimulants of adenosine receptors, β‐adrenoceptors, GABA B receptors and intestinal vasoactive peptide (VIP), also increased basal CA secretion in a highly significant manner. However, when they were added together with forskolin, CA secretion was not affected although an additive increase in cyclic AMP levels was produced. 4 Statistical analysis of the correlation between cyclic AMP levels and CA secretion evoked by these cyclic AMP increasing compounds showed that a significant direct correlation between both parameters existed only when low levels of cyclic AMP were produced by secretogogue stimulation. When the increase in intracellular cyclic AMP concentrations exceeded approximately 8 times the basal cyclic AMP levels the correlation was not significant. These results indicate a dual dose‐dependent effect of cyclic AMP on basal CA secretion. 5 The stimulatory effect of low cyclic AMP on basal CA secretion was accompanied by an increase in membrane potential and in intracellular calcium concentrations ([Ca 2+ ] i ), the latter mainly being due to an increase in intracellular Ca 2+ entry through L‐type voltage‐dependent Ca 2+ channels. 6 The possible mechanisms involved in these cyclic AMP effects are discussed.