Interaction of epinephrine with isolated rabbit tracheal epithelial cells

l-Epinephrine-mediated effects on intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels in rabbit surface tracheal epithelial cells (tracheocytes) were investigated to understand the difference in potency of epinephrine and isoproterenol compared with that observed in intact tracheal mucosa-submucosa. Epinephrine-mediated increases in cAMP levels reached a maximum in approximately 10 min then decreased; however, cAMP levels remained elevated even after 30 min of incubation with catecholamine. The beta-adrenergic antagonist propranolol partially blocked the dose-dependent increase in cAMP caused by epinephrine. Phentolamine, an alpha-adrenergic antagonist, and inhibitors of cyclooxygenase (ibuprofen, indomethacin, and acetylsalicylic acid) caused a shift to the right of the epinephrine dose-response curve, indicating antagonism of the response to epinephrine. Epinephrine, but not isoproterenol, stimulated the generation and release of prostaglandin (PG) E2, with 1.1 microM producing a half-maximal effect. This effect was antagonized by ibuprofen, phentolamine, and yohimbine, an alpha 2-adrenergic antagonist, but not by propranolol. The alpha 2-adrenergic effect of epinephrine was mimicked by clonidine, which stimulated PGE2 generation and release and caused an increase in cAMP levels in a dose-dependent manner; its effects on PGE2 release were blocked by ibuprofen and yohimbine. Methoxamine, an alpha 1-adrenergic agonist, did not stimulate PGE2 release. PGE2 alone caused a time- and dose-dependent increase in cAMP levels. In the presence of clonidine and isoproterenol, PGE2 was released, and the dose-dependent increase in cAMP levels mediated by isoproterenol was shifted to the left, indicating increased potency.(ABSTRACT TRUNCATED AT 250 WORDS)