Physiological approach of beta receptor coupling to adenylate cyclase in rat airways: ontogenical modification and functional antagonism.
The relaxant effects of isoproterenol, forskolin and sodium nitroprusside were studied on tracheal pieces and lung parenchymal strips of Sprague-Dawley and Wistar rats according to age and functional antagonism with carbachol applied previously to induce the contraction. The beta receptor-related maximal relaxant effect of isoproterenol decreased from 4 to 11 weeks in Sprague-Dawley rat airways contracted with 10(-6) M carbachol. This maximal relaxant effect did not change with age in the Wistar strain. When lower carbachol concentrations were applied to Wistar trachea, the maximal relaxant effect of isoproterenol raised with a large decrease of the EC50 values. In the Sprague-Dawley strain, a similar diminution of carbachol concentration also allowed to increase the maximal amplitude of relaxation, but a smaller decrease of EC50 was observed as referred to the Wistar strain. These results suggest that the decrease with age of the maximal relaxation of Sprague-Dawley airways by isoproterenol might be linked to impaired functional antagonism between beta adrenergic and muscarinic stimulation in this rat strain. This hypothesis was strengthened by the observation of the effects of forskolin, an activator of adenylate cyclase, and sodium nitroprusside, a cyclic GMP-related relaxant drug, that did not show any modified effect in function of age in both rat strains. A modified regulation of adenylate cyclase complex with ontogenesis and with rat strain is suggested.
Frossard
N
N
Landry
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000367:Age Factors; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014132:Trachea / Q000502:physiology*
D004224:Diterpenes; D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D005576:Colforsin; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D007545:Isoproterenol