Role of protein kinase C in calcium sensitization during muscarinic stimulation in airway smooth muscle.
Muscarinic receptor stimulation increases Ca2+ sensitivity, i.e., the amount of force produced at a constant submaximal cytosolic Ca2+ concentration ([Ca2+]i), in permeabilized smooth muscle preparations. It is controversial whether this increase in Ca2+ sensitivity is in part mediated by protein kinase C (PKC). With the use of a beta-escin permeabilized canine tracheal smooth muscle (CTSM) preparation, the effect of four putative PKC inhibitors [calphostin C, chelerythrine chloride, a pseudosubstrate inhibitor for PKC [PKC peptide-(19-31)], and staurosporine] on Ca2+ sensitization induced by acetylcholine (ACh) plus GTP was determined. Preincubation with each of the inhibitors did not affect subsequent Ca2+ sensitization induced by muscarinic receptor stimulation in the presence of a constant submaximal [Ca2+]i, neither did any of these compounds reverse the increase in Ca2+ sensitivity induced by ACh plus GTP. Administration of a 1,2-diacylglycerol analog, 1-oleoyl-2-acetyl-sn-glycerol, did not induce Ca2+ sensitization at a constant submaximal [Ca2+]i. Thus we found no evidence that PKC mediates increases in Ca2+ sensitivity produced by muscarinic receptor stimulation in permeabilized CTSM.
Bremerich
D H
DH
Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Warner
D O
DO
Lorenz
R R
RR
Shumway
R
R
Jones
K A
KA
D000109:Acetylcholine / Q000494:pharmacology*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002463:Cell Membrane Permeability; D003600:Cytosol / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004928:Escin; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004075:Diglycerides; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010446:Peptide Fragments; D010617:Phenanthridines; D011976:Receptors, Muscarinic; D004928:Escin; D006160:Guanosine Triphosphate; C038237:1-oleoyl-2-acetylglycerol; C016299:chelerythrine; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D000109:Acetylcholine; D002118:Calcium