AJP - Endocrinology and Metabolism, Vol 271, Issue 3 E556-E562, Copyright © 1996 by American Physiological Society
Modulation of beta-adrenergic receptor-stimulated lipolysis in the heart by prostaglandins
Y. Ruan, H. Kan, C. Cano and K. U. Malik
Department of Pharmacology, School of Medicine, University of Tennessee, Memphis 38163, USA.
The purpose of the present study was to investigate the contribution of
prostaglandins to lipolysis elicited by beta-adrenergic receptor activation
in the heart. We have studied the effect of prostaglandin E2 (PGE2),
prostaglandin I2 (PGI2), and their precursor arachidonic acid (AA) in the
presence and absence of a cyclooxygenase inhibitor, sodium meclofenamate,
on glycerol output elicited by stimulation of beta-adrenergic receptors in
the isolated rabbit heart with isoproterenol (ISOP). Bolus injections of
ISOP (475 pmol) produced a constant increase in glycerol and
6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output. Infusion of sodium
meclofenamate (16 microM) reduced basal and attenuated ISOP-induced
6-keto-PGF1 alpha output and enhanced glycerol output. During inhibition of
endogenous prostaglandin synthesis with meclofenamate, infusion of PGI2 or
PGE2 (0.1-1 microM) inhibited ISOP-induced glycerol output. Infusion of AA
(0.1-1 microM) increased 6-keto-PGF1 alpha and reduced glycerol output.
Infusion of sodium meclofenamate abolished the effect of AA to increase
6-keto-PGF1 alpha and to decrease glycerol output. These data suggest that
prostaglandins synthesized in the heart act as an inhibitory modulator of
beta-adrenergic receptor-stimulated cardiac lipolysis.
