title: Convergence of cAMP and phosphoinositide pathways during rat parotid secretion.
abstract: Rat parotid acinar cells were employed to investigate the mechanism by which receptor agonists that activate the phosphoinositide pathway enhance the stimulatory effects of adenosine 3',5'-cyclic monophosphate (cAMP) on amylase secretion. Norepinephrine (NE), which activates both alpha- and beta-adrenoceptors, evoked a secretory response that was greater than the sum of the responses obtained when NE was employed as a beta-agonist (in the presence of prazosin) and as an alpha-agonist (in the presence of propranolol). The enhancement of amylase secretion induced by NE was accompanied by an augmented rise in Ca2+ influx, as determined by fura-2 analysis. NE-induced cAMP production was comparable to that evoked by NE as a beta-agonist, and the accumulation of [3H]inositol 1,4,5-trisphosphate (IP3) evoked by NE was comparable to that elicited by NE as an alpha-agonist. The beta-adrenoceptor agonist isoproterenol potentiated the rise in cytosolic Ca2+ elicited by the muscarinic agonist carbachol, while possessing no stimulatory effect of its own. Isoproterenol had no effect on carbachol-induced stimulation of [3H]IP3 or 1,3,4,5-[3H]inositol tetrakisphosphate accumulation. Ionomycin and dibutyryl cAMP in combination produced a similar enhancing effect on the Ca2+ signal and amylase release as adrenergic and muscarinic receptor agonists. These results suggest that the synergism between the phosphoinositide and cAMP-signaling systems in parotid cells resides in enhanced Ca2+ availability.
authors: Department of Pharmacology, Medical College of Virginia, Richmond 23298.
authors: J S
authors: JS
authors: McKinney
authors: M S
authors: MS
authors: Desole
authors: R P
authors: RP
authors: Rubin
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D001572:Benzofurans; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction
chemical_list: D001572:Benzofurans; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D003994:Bucladesine; D011433:Propranolol; D000242:Cyclic AMP; D000681:Amylases; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine