AJP - Lung Cellular and Molecular Physiology, Vol 259, Issue 4 198-L205, Copyright © 1990 by American Physiological Society
Alpha-adrenergic regulation of secretion by tracheal glands
D. J. Culp, R. K. McBride, L. A. Graham and M. G. Marin
Department of Dental Research, University of Rochester School of Medicine and Dentistry, New York 14642.
The purpose of the present study was to begin to characterize,
pharmacologically, the alpha-adrenergic regulation of glycoconjugate
secretion from airway glands. Using isolated gland cells from cat trachea,
we determined the binding characteristics of [3H]dihydroergocryptine
([3H]DHE), an alpha-adrenergic antagonist, with equal affinities for alpha
1- and alpha 2-adrenergic receptors. Specific binding of [3H]DHE to gland
cell homogenates was saturable, of high affinity (KDapp = 4.2 nM) and
inhibited with greater efficacy by epinephrine much greater than
isoproterenol. Competition experiments with alpha 1- and alpha 2-adrenergic
selective antagonists (prazosin and yohimbine, respectively) demonstrated
high- and low-affinity sites for each antagonist, indicating the presence
of both receptor subtypes. In studies of glycoconjugate secretion by cat
tracheal explants, secretion was stimulated by adrenergic agonists with the
rank potency: norepinephrine greater than or equal to phenylephrine greater
than epinephrine much greater than clonidine. alpha-Adrenergic-stimulated
secretion (epinephrine + propranolol) was inhibited by low concentrations
of prazosin, but was unaffected by 100 nM yohimbine. The alpha 2-adrenergic
agonists, clonidine and UK-14,304, each markedly inhibited
beta-adrenergic-stimulated secretion. Collectively, these results
demonstrate alpha 1-adrenergic regulation of glandular glycoconjugate
secretion and suggest alpha 2-adrenergic receptors may modulate
beta-adrenergic-stimulated secretion.
