Adrenergic nervous control of cAMP-mediated amylase secretion in the rat pancreas.
In this study of nervous control of exocrine secretion, electrical field stimulation (FS) evoked a marked, tetrodotoxin-sensitive increase in the amylase output from in vitro segments of rat pancreas. Blockade of the large cholinergic component of the response by atropine revealed a smaller noncholinergic nerve-mediated secretion. This noncholinergic secretion was unaffected by phentolamine but abolished by propranolol, as were the secretory responses to norepinephrine and other beta-adrenergic agonists. FS also produced an increase in the efflux of radiolabeled norepinephrine from preloaded tissue that was tetrodotoxin sensitive and calcium dependent. Although FS and the adrenergic secretagogues had no effect on 45Ca2+ metabolism or acinar cell electrical properties of atropine-treated rat pancreas, they both evoked increases in tissue cAMP levels. These increases in cAMP concentration were also blocked by propranolol. The phosphodiesterase inhibitor isobutylmethylxanthine potentiated both the elevation of cAMP levels and the amylase secretion evoked by adrenergic stimulation. Since both specific beta 1- and beta 2-adrenergic agonists elevated cAMP levels and caused amylase secretion, it appears that both beta-receptor subtypes are present in the rat pancreas. Of the selective beta 1- and beta 2-antagonists used, the most pronounced reduction, but not complete blockade, of the FS- and norepinephrine-induced cyclic nucleotide and secretory effects was obtained with the beta 1-antagonist metoprolol. It is concluded that stimulation of adrenergic nerves in the rat pancreas evokes an amylase secretion that is mediated via the activation of mainly beta 1-type adrenergic receptors and the utilization of cAMP as an intracellular second messenger.
D000109:Acetylcholine / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000294:innervation*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D010656:Phenylephrine; D013779:Tetrodotoxin; D011433:Propranolol; D000242:Cyclic AMP; D000681:Amylases; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine