Changes in cytosolic CA2+ and contraction induced by various stimulants and relaxants in canine tracheal smooth muscle.
Effects of stimulants and relaxants on the cytosolic Ca2+ level [(Ca2+]cyt) and contraction were examined in isolated canine tracheal smooth muscle. High K+ and carbachol induced a sustained increase in [Ca2+]cyt and muscle tension. Cumulative addition of KCl induced a graded increase in [Ca2+]cyt and muscle tension. Cumulative addition of carbachol induced greater contraction than high K+ at a given [Ca2+]cyt 12-Deoxyphorbol 13-isobutyrate (DPB) (50 nmol/l) induced a small sustained contraction with little effect on [Ca2+]cyt. A higher concentration (1 mumol/l) of DPB induced a larger sustained contraction with a decrease in [Ca2+]cyt. DPB (50 nmol/l) potentiated the KCl-induced contraction without or with only a small additional increase in [Ca2+]cyt. By contrast, 1 mumol/l DPB potentiated the high-K(+)-induced contraction with a decrease in [Ca2+]cyt. Addition of 50 nmol/l or 1 mumol/l DPB in the presence of carbachol inhibited both [Ca2+]cyt and muscle tension. Verapamil, isoprenaline and forskolin did not change or slightly decreased [Ca2+]cyt and muscle tension in resting trachea. Verapamil inhibited the contraction and [Ca2+]cyt stimulated by high K+ and carbachol. Isoprenaline and forskolin inhibited the high-K(+)-induced contraction without changing [Ca2+]cyt, whereas these inhibitors inhibited carbachol-induced contraction with a relatively small decrease in [Ca2+]cyt. These results suggest that (a) sustained contractions induced by high K+ and carbachol are due to the sustained increase in [Ca2+]cyt, (b) carbachol increases the sensitivity of contractile elements to Ca2+, and (c) isoprenaline and forskolin inhibit the contraction by the decrease in [Ca2+]cyt and also by the decrease in the sensitivity of contractile elements to Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
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Ozaki
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Kwon
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Tajimi
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Karaki
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism*; D004285:Dogs; D016257:Fura-2; D007545:Isoproterenol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D014132:Trachea / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D001572:Benzofurans; D010703:Phorbol Esters; D005576:Colforsin; D002217:Carbachol; D014700:Verapamil; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium; D016257:Fura-2