Phosphoinositide synthesis in desensitized rat pancreatic acinar cells.
To help understand the possible role of phosphoinositide turnover in the desensitization process, the availability of phosphatidylinositol 4,5-bisphosphate was investigated in normal and desensitized pancreatic acinar cells treated with carbamylcholine (Cch), caerulein (Cae), and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In control acini, incorporation of [myo-3H]inositol into total phosphoinositides was maximal at 120 min, was Cch and Cae dose dependent, and was insensitive to TPA. Cch stimulation increased the proportion of [myo-3H]inositol incorporated into phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], whereas Cae specifically channeled [myo-3H]inositol incorporation into phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. In the desensitized cells, preexposure to Cch and Cae, but not to TPA, increased the subsequent basal rate of [myo-3H]inositol incorporation into total phosphoinositol (PI) by 66 and 50% above control values. There were no subsequent responses to increasing concentrations of Cch, Cae, and TPA during a second incubation. Desensitization of the pancreatic secretory responses to Cch, Cae, and TPA does not seem to result from a decrease either in total PI or in specific PtdIns(4,5)P2 synthesis, which is needed for inositol trisphosphate and diacylglycerol production.
Lods
J S
JS
Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Quebec, Canada.
Rossignol
B
B
Dreux
C
C
Morisset
J
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002108:Ceruletide / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C060974:phosphatidylinositol 3,4,5-triphosphate; C060980:phosphatidylinositol 3,4-diphosphate; D014316:Tritium; D007294:Inositol; D002108:Ceruletide; D002217:Carbachol; D013755:Tetradecanoylphorbol Acetate