Calcium oscillations in guinea-pig pancreatic acinar cells exposed to carbachol, cholecystokinin and substance P.
1. Cytoplasmic Ca2+ ([Ca2+]i) responses were studied in guinea-pig pancreatic acinar cells during stimulation with cholecystokinin octapeptide (CCK-8), substance P (SP) and carbachol. 2. Individual cells exhibited [Ca2+]i responses to all three agonists. 3. In the absence of external Ca2+, all the agonists initiated [Ca2+]i peaks which, particularly at high agonist concentrations, rapidly declined. 4. SP induced repetitive monophasic [Ca2+]i transients which started from basal [Ca2+]i even after elevation of the external Ca2+ concentration. 5. CCK-8 triggered similar oscillations, which particularly at high agonist concentration or after elevating external Ca2+ became superimposed upon a sustained elevation of [Ca2+]i. 6. Carbachol-induced oscillations were more complex with [Ca2+]i transients superimposed on slower waves. 7. At high carbachol concentrations or elevation of external Ca2+ the slow waves fused into a sustained increase of [Ca2+]i. 8. The protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate attenuated the agonist-induced [Ca2+]i responses, and this effect was reversed by the PKC activator staurosporine. 9. The results indicate that oscillations of [Ca2+]i induced by SP, CCK-8 and carbachol involve intracellular mobilization of Ca2+. 10. CCK-8 and carbachol also cause a rise of [Ca2+]i by a mechanism more directly dependent on the presence of extracellular Ca2+. 11. In the case of carbachol the latter component is subject to oscillatory control. 12. The transition from oscillatory [Ca2+]i to sustained increase may be associated with inhibition of amylase release.
Sjödin
L
L
Pharmacological Division, Medical Products Agency, Uppsala, Sweden.
Dahlén
H G
HG
Gylfe
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D002217:Carbachol; D002766:Cholecystokinin; D002118:Calcium