Role of protein kinase C in calcium sensitization during muscarinic stimulation in airway smooth muscle.

Academic Article

Abstract

  • 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.
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    Keywords

  • Acetylcholine, Alkaloids, Animals, Benzophenanthridines, Calcium, Cell Membrane Permeability, Cytosol, Diglycerides, Dogs, Enzyme Inhibitors, Escin, Female, Guanosine Triphosphate, In Vitro Techniques, Kinetics, Male, Muscle Contraction, Muscle, Smooth, Naphthalenes, Peptide Fragments, Phenanthridines, Protein Kinase C, Receptors, Muscarinic, Staurosporine, Trachea
  • Digital Object Identifier (doi)

    Author List

  • Bremerich DH; Warner DO; Lorenz RR; Shumway R; Jones KA
  • Start Page

  • L775
  • End Page

  • L781
  • Volume

  • 273
  • Issue

  • 4