Protein kinase C modulators enhance angiotensin II desensitization of guinea pig ileum via maxi-K+ channels

Abstract

We investigated the role of protein kinase in the desensitization of the angiotensin II induced contraction of guinea pig ileum. in contrast to their antagonistic effects on enzymatic activity, body activation blockers accelerated the dissipation of the 10(-7) M angiotensin II isometric contractile response. These agents indirectly activated maxi-K- channels in cell-attached membrane patches from freshly dispersed myocytes bathed in high-K- solution and clamped at -40 mV. in parallel with the contractile responses, fura 2-loaded myocytes bathed in Tyrode solution showed additive increases in [Ca2+] in response to both angiotensin II and phorbol dibutyrate (PDB). the PDB-promoted increase of the rate of angiotensin II desensitization was completely abolished by pretreatment of the tissue strips with 93 nM iberiotoxin or 8 mM KCl. Thus, we conclude that protein kinase C modulators promote faster angiotensin II desensitization by recruiting maxi-K- channels and inducing membrane repolarization rather than by affecting the protein kinase C activity. (C) 2002 Elsevier Science B.V. All rights reserved.