Mechanism of regulation of amylase release by .ALPHA.- and .BETA.-adrenergic agonists in rat parotid tissue.

Abstract

The effect of forskolin and isobutyl-methylxanthine on amylase release and cyclic AMP accumulation by a-and f-adrenergic agonists was studied in rat parotid slices. A small increase in cyclic AMP by ~3-adrenergic agonists was sufficient for maximum stimulation of amylase release (YOSHIMURA et al., 1982a), but a similar increase in cyclic AMP by forskolin did not stimulate the maximum amount of amylase release. The amount of amylase release and cyclic AMP changed in parallel when lower doses of isobutyl-methylxanthine were used, but higher doses of isobutyl-methylxanthine further increased cyclic AMP without causing a significant increase in amylase release. Amylase release stimulated to its maximum by isobutyl-methylxanthine was much lower than that by isoproterenol. These results suggest that cyclic AMP is not the only chemical correlate for the activation of amylase release by ~-adrenergic agonists. The effect of phenylephrine and methoxamine on amylase release was augmented by either forskolin or isobutyl-methylxanthine, but the effect of methacholine was not. Phenylephrine increased the cyclic AMP concentration under the same conditions, but methoxamine did not. The inhibition of the effect of phenylephrine plus forskolin on cyclic AMP accumulation by propranolol was almost complete and stereospecific, but the inhibition of their effects on amylase release was incomplete and not stereospecific. Synergism of amylase release was observed in the effect between methoxamine and dibutyryl-cyclic AMP. These results suggest that the augmentation of the effect of a-adrenergic agonists on amylase release by forskolin or isobutyl-methylxanthine cannot be explained only on changes in cyclic AMP and that some other factor in collaboration with cyclic AMP may participate in the regulation of amylase release by aadrenergic agonists.

Augmentation of isoproterenol-stimulated tissue cyclic AMP level by cholinergic agonists in rat parotid gland.

“…Forskolin also acts to augment hormone-stimulated cyclic AMP production in many tissues (SERMON and DALY, 1981;SERMON et al, 1981). In the parotid gland, our report stipulates that forskolin increases the level of cyclic AMP and potentiates the effect of isoproterenol on tissue cyclic AMP accumulation (YosHIMURA et al, 1984b). The effect of forskolin on cellular cyclic AMP accumulation, however, was not potentiated by either A23187 or oxotremorine, although its effect was augmented by isobutylmethylxanthine.…”

“…Male Wistar rats (200-450 g), normally fed, were killed by cervical dislocation, and the parotid gland was rapidly excised, trimmed of fat and connective tissues and sliced by hand with a razor blade. About 0.5 mm thick slices were put into a flask containing 1 ml of modified Krebs Henseleit phosphate buffer, pH 7.4, 1.03 mM CaC12, 1 mg/ml bovine albumin and 10 mM glucose, as described previously (YOSHIMURA et a!., 1984b), with pure oxygen used as the gas phase. After being weighed (about 20 mg per flask), the slices were preincubated for 10 min by shaking at 37°C.…”

Cyclic AMP has distinct effects from Ca 2+ in evoking priming and fusion/exocytosis in parotid amylase secretion

“…These results suggest that the mechanisms by which isoproterenol and CCh regulate amylase secretion are different. Several studies have shown a potentiation of amylase secretion induced by combined stimulation with cAMPand Ca 2+ -mediated agonists [8,15,16,17,19,20]. However, the role of these two messengers in the mechanism of potentiation has not yet been clarified.…”

Carbachol‐induced [Ca2+]i increase, but not activation of protein kinase C, stimulates exocytosis in rat parotid acini

“…Another mechanism to stimulate amylase secretion is activated by Ca 2+ ‐mobilizing agonists such as muscarinic cholinergic, α‐adrenergic and substance P receptor stimulants. Since the removal of extracellular Ca 2+ causes a large reduction in amylase secretion induced by these agonists (Putney et al 1977; Watson et al 1979; Yoshimura et al 1984), changes in [Ca 2+ ] i have been assumed to be crucial to the effects of these agonists. However, the precise role of [Ca 2+ ] i in the regulation of amylase secretion has still not been fully elucidated.…”