Convergence of cAMP and phosphoinositide pathways during rat parotid secretion.
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.
McKinney
J S
JS
Department of Pharmacology, Medical College of Virginia, Richmond 23298.
Desole
M S
MS
Rubin
R P
RP
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
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