Cyclic AMP regulation of calcium mobilization and amylase release from isolated permeabilized rat parotid cells.
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.
Rubin
R P
RP
Department of Pharmacology & Therapeutics, State University of New York at Buffalo.
Adolf
M A
MA
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
D013729:Terpenes; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D000242:Cyclic AMP; D000681:Amylases; D002118:Calcium