Protein kinase C regulates the tonic but not the phasic component of contraction in guinea-pig ileum

T. Sasaguri, S. P. Watson

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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+. 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, 4α-phorbol, which does not activate protein kinase C, had no effect on these responses. Exposure to phorbol 12-myristate 13-acetate (PMA; 1 μM) 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. 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. 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+.

Original languageEnglish
Pages (from-to)791-798
Number of pages8
JournalBritish Journal of Pharmacology
Volume98
Issue number3
DOIs
Publication statusPublished - 1989
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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