Neurohormonal receptors and cyclic AMP-binding proteins in rabbit tracheal mucosa-submucosa.
Neurohormones and drugs that alter in vitro tracheal electrolyte transport and mucus glycoprotein secretion were examined for their ability to alter cyclic nucleotide accumulation in a smooth muscle-free preparation of rabbit tracheal mucosa-submucosa. cAMP levels were increased by beta-adrenergic agonists, histamine, 2-Cl-adenosine and prostaglandin E1. cGMP levels were increased by carbachol. The phosphodiesterase inhibitor isobutylmethylxanthine increased cAMP and cGMP levels and potentiated only the beta-adrenergic effects. The beta-adrenergic effects were blocked by (+/-)-propranolol and the effects of histamine by diphenhydramine, atropine and (+/-)-propranolol. Atropine blocked the carbachol effects. The isolated surface epithelium from rabbit trachea had higher basal cAMP levels and greater response to beta-adrenergic agonists and isobutylmethylxanthine than the mucosa-submucosa. Two major cAMP-binding proteins in the tracheal mucosa-submucosa were identified with the photoaffinity label 8-N3-[32P]cAMP. Agents that increased cAMP levels also decreased photoaffinity labelling, suggesting that these two cAMP-binding proteins were being occupied in the intact cell. The molecular weights of the proteins were 50 000 and 54 000 and correspond in electrophoretic mobility to the regulatory subunits of Type-I and Type-II cAMP-dependent protein kinases, respectively. The results are consistent with the hypothesis that epithelial functions in the airways are modulated by a number of agonists which increase cyclic nucleotide levels. The effects of beta-adrenergic agonists is apparently mediated by activation of adenylate cyclase and subsequent activation of cAMP-dependent protein kinases.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein; D006152:Cyclic GMP / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011953:Receptors, Cyclic AMP / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D011956:Receptors, Cell Surface; D011953:Receptors, Cyclic AMP; D006632:Histamine; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol