Phorbol ester attenuates inositol 1,4,5-trisphosphate-induced Ca2+ release in electropermeabilized rat pancreatic acini. 1992

Y Arita, and T Kimura, and Y Ogami, and H Nawata
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009712 Nucleotides, Cyclic Cyclic Nucleotide,Cyclic Nucleotides,Nucleotide, Cyclic
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D006493 Heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer

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