Protein kinase C activators inhibit the inositol trisphosphate-mediated muscarinic current responses in rat lacrimal cells

J Physiol. 1987 Dec;394:239-48. doi: 10.1113/jphysiol.1987.sp016868.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Calcium / metabolism
  • Electrophysiology
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / pharmacology
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate
  • Inositol Phosphates / pharmacology*
  • Lacrimal Apparatus / cytology
  • Lacrimal Apparatus / drug effects*
  • Lacrimal Apparatus / physiology
  • Protein Kinase C / physiology
  • Rats
  • Sugar Phosphates / pharmacology*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Thionucleotides / pharmacology

Substances

  • Inositol Phosphates
  • Sugar Phosphates
  • Thionucleotides
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Inositol 1,4,5-Trisphosphate
  • Guanosine Triphosphate
  • Protein Kinase C
  • Acetylcholine
  • Tetradecanoylphorbol Acetate
  • Calcium