Inhibitory effects of Gs on desensitization of beta-adrenergic receptors in tracheal smooth muscle.
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.
Kume
H
H
Second Department of Internal Medicine, School of Medicine, Nagoya University, Japan.
Takagi
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000819:agonists; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D016210:Methacholine Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014132:Trachea / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D013873:Thionucleotides; D016210:Methacholine Chloride; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D002772:Cholera Toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D007545:Isoproterenol