Protein kinase C modulators enhance angiotensin II desensitization of guinea pig ileum via maxi-K+ channels.
We investigated the role of protein kinase C in the desensitization of the angiotensin II-induced contraction of guinea pig ileum. In contrast to their antagonistic effects on enzymatic activity, both activator and 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+]i 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.
Aboulafia
Jeannine
J
Department of Biophysics, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu, SP, São Paulo, Brazil.
Silva
Bagnólia A
BA
Nouailhetas
Viviane L A
VL
D000470:Alkaloids; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010617:Phenanthridines / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010617:Phenanthridines; D024681:Potassium Channels, Calcium-Activated; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; C016299:chelerythrine; D011493:Protein Kinase C