Beta-adrenergic modulation of mucin secretion in cat trachea.
The mechanism of beta-adrenergic regulation of mucin secretion was investigated in cat trachea in vitro. beta-Adrenergic agonists increased the release of [35S]SO4-radiolabeled mucin and mucosa-submucosal adenosine 3',5'-cyclic monophosphate (cAMP) levels in a dose- and time-dependent manner. The relative potencies and efficacies of l-isoproterenol, l-epinephrine, l-norepinephrine, terbutaline, and dobutamine for physiological and biochemical events were similar. The effect of these agonists were blocked by d-l-propranolol. 3-Isobutyl-l-methylxanthine (IBMX) and 8-bromo-cAMP mimicked the effects of the agonists on mucin release. IBMX increased cAMP levels and potentiated the increase in cAMP levels effected by beta-adrenergic agonists. The half-maximal effects of l-isoproterenol on cAMP levels and mucin release were attained at 1.6 and 8.8 min, respectively. Three major mucosa-submucosal proteins of apparent molecular weights of 49,000, 54,000, and 59,000 daltons displayed reduced binding of the photoaffinity label 8-N3-[32P]cAMP when endogenous cAMP levels were increased with l-isoproterenol and/or IBMX. The first two proteins correspond in electrophoretic mobility to the regulatory subunits of type I and type II cAMP-dependent protein kinases, respectively. The 59,000-dalton cAMP binding protein may be the phosphorylated form of the regulatory subunit of type II cAMP-dependent protein kinase. These data are consistent with the hypothesis that beta-adrenergic modulation of tracheal mucin release is mediated by cAMP and suggest that activation of cAMP-dependent protein kinases may be involved in the neurohormonal effects.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009077:Mucins / Q000378:metabolism*; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D014132:Trachea / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D009077:Mucins; D013431:Sulfates; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine