Phorbol ester attenuates inositol 1,4,5-trisphosphate-induced Ca2+ release in electropermeabilized rat pancreatic acini.
To investigate the mechanism of inositol trisphosphate (IP3)-induced Ca2+ release from the internal Ca2+ store, we examined the effects of heparin, phorbol ester and cyclic nucleotides on Ca2+ release induced by carbachol or inositol 1,4,5-trisphosphate (1,4,5-IP3). For monitoring changes of Ca2+ we used the fluorescent indicator, fura-2, in electropermeabilized rat pancreatic acini. An amount of 100 micrograms/ml heparin inhibited the Ca2+ release induced by 1 microM 1,4,5-IP3 in permeabilized acini. Pretreatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 10 min reduced the release of Ca2+ induced by 10 microM carbachol and 1 microM 1,4,5-IP3 in permeabilized acini. Staurosporine, a protein kinase C inhibitor, blocked the inhibitory effect of TPA. Cytosolic calcium concentration was restored by staurosporine in TPA-treated acini. Although cyclic AMP exaggerated the amylase release induced by carbachol, cyclic AMP and cyclic GMP had no effect on the carbachol-induced release of Ca2+ in permeabilized acini. These findings suggest that protein kinase C may act at the level of the IP3 receptors or the IP3-operated Ca2+ channels of the internal Ca2+ store and indicate that cyclic nucleotides do not affect the IP3-induced release of Ca2+ in rat pancreatic acini.
Arita
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kimura
T
T
Ogami
Y
Y
Nawata
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability; D016257:Fura-2; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008297:Male; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015220:Calcium Channels; D009712:Nucleotides, Cyclic; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D006493:Heparin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2