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J. Biol. Chem., Vol. 262, Issue 16, 7447-7450, Jun, 1987
D Sugden and DC Klein
The adrenergic regulation of cyclic GMP in isolated pinealocytes was
investigated. In this cell, norepinephrine stimulates cyclic GMP and cyclic
AMP greater than 100-fold by activating both alpha 1- and beta-
adrenoceptors. beta-Adrenergic activation is a requisite event and is
potentiated by alpha 1-adrenergic activation (Vanecek, J., Sugden, D.,
Weller, J. L., and Klein, D. C. (1985) Endocrinology 116, 2167-2173). The
current study found that cholera toxin could substitute for beta-
adrenergic agonists in stimulating pinealocyte cyclic GMP content, as has
been found to be the case for cyclic AMP. Treatment with cholera toxin
alone (1 microgram/ml for 90 min) had a small effect (2- to 4- fold
increase) on cyclic GMP; addition of the alpha 1-adrenergic agonists,
phenylephrine, cirazoline, or methoxamine to cholera toxin- treated cells
rapidly (peak at 5 min) caused a further 30- to 300-fold increase. The
alpha 1-adrenergic agonists had little effect by themselves at
concentrations which potentiated the effects of cholera toxin. The
potentiating effect of phenylephrine was inhibited nearly completely by an
alpha 1-adrenergic antagonist, but not by either an alpha 2- or
beta-adrenergic antagonist. The purified cholera toxin subunits A and B did
not stimulate cyclic GMP either alone or in the presence of phenylephrine.
Furthermore, the potentiating action of phenylephrine was observed
following 90 min but not 20 min of cholera toxin pretreatment. these
results suggest that the regulation of cyclic GMP levels in the pineal
gland involves an Ns-like GTP-binding regulatory protein. This is of
interest because it is the first indication that cyclic GMP is regulated by
such a GTP-binding protein in nonretinal tissue. It remains to be
determined whether the mechanisms involved in the transmembrane regulation
of cyclic AMP and cyclic GMP in any other tissue are similar.
A cholera toxin substrate regulates cyclic GMP content of rat pinealocytes
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S. L. Coon, S. K. McCune, D. Sugden, and D. C. Klein Regulation of Pineal alpha 1B-Adrenergic Receptor mRNA: Day/Night Rhythm and beta -Adrenergic Receptor/Cyclic AMP Control Mol. Pharmacol., April 1, 1997; 51(4): 551 - 557. [Abstract] [Full Text] |
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