title: Cyclic AMP regulation of calcium mobilization and amylase release from isolated permeabilized rat parotid cells.
abstract: This study examined the mechanistic basis of the synergistic interaction between the cyclic AMP (cAMP) and phosphoinositide pathways in salivary amylase secretion. cAMP produced a concentration-dependent increase in Ca++ mobilization from saponin-permeabilized rat parotid acinar cells. A threshold concentration of cAMP (50 microM) significantly increased the peak Ca(++)-releasing activity of submaximal concentrations of inositol 1,4,5-trisphosphate (IP3) but did not augment the Ca++ mobilization induced by a maximal stimulating concentration of IP3 (30 microM). A maximal stimulating concentration of cAMP (500 microM) failed to modify the Ca++ releasing action of IP3. IP3-induced Ca++ release was also augmented by catalytic subunit of cAMP-dependent protein kinase. A specific protein kinase inhibitor reversed this effect. The cAMP-induced Ca++ release was blocked by ryanodine but not by heparin, by contrast with the IP3-induced Ca++ release. Thapsigargin only partially depressed the cAMP response but completely abolished the IP3 response. The amylase release elicited by fixed concentrations of Ca++ was not further enhanced by either cAMP or forskolin. Thus, unlike diacylglycerol, which decreases the Ca++ requirement for secretion by inducing activation of protein kinase C, cAMP appears to mediate salivary amylase secretion by regulating the sensitivity of parotid cells to the Ca++ mobilizing action of IP3. In addition, cAMP possesses a second action, i.e., directly eliciting Ca++ mobilization from an IP3-insensitive pool.
authors.affiliation: Department of Pharmacology & Therapeutics, State University of New York at Buffalo.
authors.forename: R P
authors.initials: RP
authors.lastname: Rubin
authors.forename: M A
authors.initials: MA
authors.lastname: Adolf
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008297:Male; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D013729:Terpenes; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D000242:Cyclic AMP; D000681:Amylases; D002118:Calcium