AJP - Lung Journal of Applied Physiology
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Am J Physiol Lung Cell Mol Physiol 273: L556-L564, 1997;
1040-0605/97 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 3 556-L564, Copyright © 1997 by American Physiological Society

ARTICLES

Inhibitory effects of Gs on desensitization of beta-adrenergic receptors in tracheal smooth muscle

H. Kume and K. Takagi
Second Department of Internal Medicine, School of Medicine, Nagoya University, Japan.

We examined the reduction of mechanical responsiveness to beta-agonists after continuous or repeated exposure to agonists in guinea pig tracheal smooth muscle, using an isometric tension record. The inhibitory action of 0.1 microM isoproterenol (Iso) on contraction induced by 1 microM methacholine (MCh) was suppressed markedly after incubation with 0.0003-3 microM Iso for 1 h. The effects of Iso on MCh-induced contraction gradually decreased after repeated application of these agents at intervals of 1 h. When Iso was perfused cumulatively to tissues repeatedly precontracted by MCh, the effects of Iso were reduced at the second application. This reduced responsiveness to beta-agonists was not mimicked by forskolin and did not occur after preexposure of the strips to 2 micrograms/ml cholera toxin for 6 h. We concluded that this reduced responsiveness to beta-agonists is homologous desensitization and that the irreversible activation of the stimulatory G proteins, Gs, may play an important role in prevention of the reduced responsiveness to beta-agonists.


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