Protein kinase C activators inhibit the inositol trisphosphate-mediated muscarinic current responses in rat lacrimal cells.
1. Pre-incubation (1-5 min) with 12-O-tetradecanoylphorbol-13-acetate (TPA, 8-16 nM), a tumour-promoting phorbol ester known to activate protein kinase C, was found to inhibit acetylcholine-induced Ca2+-dependent K+ and Cl- currents in cells isolated from rat lacrimal glands. 2. Previous work showed that the same currents may be elicited by dialysing cells with a high-Ca2+ (1.0 microM) solution, with inositol trisphosphate (InsP3), or with guanosine 5'-[gamma-thio]triphosphate (GTP-gamma-S). 3. After TPA incubation both types of currents could be elicited by dialysis with elevated Ca2+ solutions, although the magnitude of the K+ current was slightly reduced in comparison with control cells. 4. Responses to intracellular dialysis with InsP3 (20 microM) were similar to those in untreated cells, indicating that the Ca2+ release process was unaffected. 5. However, the response to GTP-gamma-S (0.2-0.5 mM) dialysis was strongly inhibited in TPA-treated cells. 6. These results suggest that protein kinase C exerts an inhibitory action on the pathway leading from receptor activation to inositol trisphosphate production.
Llano
I
I
Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France.
Marty
A
A
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D007765:Lacrimal Apparatus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D013403:Sugar Phosphates / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D011493:Protein Kinase C; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium