Article date: November 1989
By: Toshiyuki Sasaguri, Stephen P. Watson in Volume 98, Issue 3, pages 791-798
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+.
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+.
DOI: 10.1111/j.1476-5381.1989.tb14607.x
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