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Apparent irrelevance of cyclic nucleotides to the relaxation of tracheal smooth muscle induced by theophylline

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Abstract

The mechanism of action of the negative inotropic (relaxing) effect of the methylxanthine theophylline on respiratory smooth muscle is generally assumed to involve inhibition of cyclic nucleotide phosphodiesterase. When guinea pig tracheal rings or dog tracheal muscle strips were incubated with low concentrations of theophylline capable of producing a significant negative inotropic effect in vivo and in vitro, there was no alteration of cyclic 3′,5′-adenosine monophosphate (cAMP) or cyclic 3′,5′-guanosine monophosphate (cGMP) levels.45Ca uptake increased however, and there was a subcellular redistribution of elemental calcium consistent with a sequestration of calcium in mitochondria and a decrease of myoplasmic calcium ion (Ca++) concentration.

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Authors and Affiliations

  1. Departments of Medicine and Pharmacology, Medical College of Georgia, 30901, Augusta, Georgia, USA

    R. C. Kolbeck, W. A. Speir, G. O. Carrier & E. D. Bransome

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  1. R. C. Kolbeck
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  2. W. A. Speir
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  3. G. O. Carrier
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  4. E. D. Bransome
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Aided in part by U. S. Public Health Service Grants No. HL-16710 and No. 5 KO7 HL 70057-Pulmonary Academic Award (to W.A.S.), American Heart Association Grant No. 76848, a Georgia Heart Association Investigatorship (to R.C.K.), and a grant from the Georgia Lung Association.

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Kolbeck, R.C., Speir, W.A., Carrier, G.O. et al. Apparent irrelevance of cyclic nucleotides to the relaxation of tracheal smooth muscle induced by theophylline. Lung 156, 173–183 (1979). https://doi.org/10.1007/BF02714008

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