Protein kinase C regulates the tonic but not the phasic component of contraction in guinea-pig ileum.
1. We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. 2. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contraction to carbachol and high K+. In contrast, 4 alpha-phorbol, which does not activate protein kinase C, had no effect on these responses. 3. Exposure to phorbol 12-myristate 13-acetate (PMA; 1 microM) for up to 8 h induced a time-dependent loss of [3H]-PDBu binding sites, consistent with the down-regulation of protein kinase C by this treatment. 4. The phasic component of contraction to carbachol or high K+ was unaffected following the down-regulation of protein kinase C. The tonic component of contraction to carbachol was markedly enhanced by this treatment while that to high K+ was partially suppressed. 5. These data suggest that although the activation of protein kinase C can lead to potentiation of the phasic component of contraction to carbachol or high K+, this appears to have little physiological significance since the response is not altered in tissues in which protein kinase C has been down-regulated. On the other hand, protein kinase C may limit the tonic contraction to carbachol but potentiate that to high K+.
Sasaguri
T
T
Department of Pharmacology, University of Oxford.
Watson
S P
SP
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*
D007295:Inositol Phosphates; D015240:Phorbol 12,13-Dibutyrate; D002217:Carbachol; D011493:Protein Kinase C; D011188:Potassium