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-opioid receptor
Department of Physiology and Institute of Cardiovascular Science and Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong
To determine whether
the phosphoinositol/Ca2+ pathway
interacts with the adenylate cyclase/adenosine 3',5'-cyclic
monophosphate (cAMP) pathway in the cardiac
-receptor, the effects
of U-50488, a specific
-receptor agonist, on the intracellular
Ca2+ concentration
([Ca2+]i)
and forskolin-induced accumulation of cAMP in rat ventricular myocytes
were determined after interference of the
phosphoinositol/Ca2+ pathway.
U-50488 suppressed the forskolin-induced accumulation of cAMP and
elevated
[Ca2+]i,
which were blocked by norbinaltorphimine, a specific
-receptor antagonist, and pertussis toxin. The effects of U-50488 were
qualitatively similar to those of A-23187, a
Ca2+ ionophore, but opposite to
those of
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester (AM), a
[Ca2+]i
chelator. Abolition of U-50488-induced elevation of
[Ca2+]i
by BAPTA-AM also abolished the effect of U-50488 on forskolin-induced accumulation of cAMP. Inhibition of the phospholipase C by specific inhibitors, U-73122 and neomycin, abolished the effects of U-50488 on
both
[Ca2+]i
and forskolin-induced accumulation of cAMP. The results showed for the
first time that
-receptor stimulation may suppress cAMP accumulation
via activation of the
phosphoinositol/Ca2+ pathway in
the rat heart.
adenylate cyclase; intracellular calcium ion; phospholipase C; ventricular myocyte; adenosine 3',5'-cyclic monophosphate
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