AJP - Cell Physiology, Vol 244, Issue 5 391-C398, Copyright © 1983 by American Physiological Society
Beta-adrenergic modulation of mucin secretion in cat trachea
C. M. Liedtke, S. A. Rudolph and T. F. Boat
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.
