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Volume 270,
Number 38,
Issue of September 22, pp. 22374-22377, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Subtype-specific
Regulation of Muscarinic Receptor Expression and Function by
Heterologous Receptor Activation
(Received for publication, March 20, 1995; and in revised form, July 20, 1995)
Darrell A.
Jackson,
Neil
M.
Nathanson
Incubation of cultured embryonic chicken heart cells with the
-adrenergic agonist isoproterenol resulted in a dose-dependent
increase in the number of mAChR on the surface of intact cells. The
isoproterenol-mediated increase in mAChR number was time dependent and
reached a maximum by 48 h. Chick heart cells treated with isoproterenol
exhibited a greater than 6-fold increase in the sensitivity for
carbachol-mediated inhibition of adenylyl cyclase activity as compared
to control. Stimulation of cultured heart cells for 24 h with
isoproterenol resulted in a 25-35% increase in cm2 mRNA levels as
compared to control cm2 mRNA levels. In contrast, the level of cm4 mRNA
was not significantly affected by isoproterenol treatment. cm2 mRNA
levels were maximally elevated by 15 h following isoproterenol
stimulation and remained elevated for up to 72 h. Incubation of cells
with isoproterenol in the presence of Rp-cAMP, an inhibitor of
cAMP-dependent protein kinase, blocked the increase in the level of cm2
mRNA. Thus, prolonged activation of -adrenergic receptors results
in an increase in mAChR number and muscarinic responsiveness in chick
heart cells due to a cAMP-dependent protein kinase mediated increase in
cm2 mRNA levels.

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Copyright © 1995 by the American Society for Biochemistry and Molecular Biology.
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