Activation of tracheal smooth muscle contraction: synergism between Ca2+ and activators of protein kinase C.
The effects of divalent ionophores (A23187 and ionomycin), Ca2+ channel agonist (BAY K 8644), and protein kinase C (C-kinase) activators [phorbol 12-myristate 13-acetate (PMA), mezerein] on bovine tracheal smooth muscle contraction were investigated. A23187 (5 microM) and ionomycin (0.5 microM) produced a prompt but transient contraction. C-kinase activators either produced no effect--e.g., PMA at 200 nM--or produced a rise in tension that was slow in onset but then gradually increased--e.g., mezerein at 400 nM. In contrast, ionophores and C-kinase activators, in combination, acted synergistically to produce a prompt and sustained contractile response that is reminiscent of that observed in response to carbachol, a cholinergic agonist. In addition, BAY K 8644 (20 nM), which has a minimal effect on tension by itself, could significantly enhance contraction induced by C-kinase activators. The contraction induced by all of these agents was quickly reversed either by removal of extracellular Ca2+ or upon addition of forskolin, an activator of adenylate cyclase. A similar reversal of carbachol-induced contraction by forskolin was observed with carbachol-induced contraction. These findings strongly suggest that C-kinase plays an important role in mediating tracheal smooth muscle contraction.
Park
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Rasmussen
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D004224:Diterpenes; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004987:Ethers / Q000494:pharmacology; D066298:In Vitro Techniques; D015759:Ionomycin; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014132:Trachea
D004224:Diterpenes; D004987:Ethers; D013729:Terpenes; D005576:Colforsin; C011309:mezerein; D000001:Calcimycin; D015759:Ionomycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium