SYNERGISM BETWEEN PROSTAGLANDIN E(2) AND ISOPROTERENOL IN STIMULATINGGLUCOSE-OXIDATION IN THE HEART

The increase in cardiac contractile function following adrenergic stim ulation is accompanied by increased glucose metabolism. Since prostagl andin E(2) (PGE(2)) can internalize beta-receptors, we determined what effects PGE(2) and isoproterenol have on glycolysis and glucose oxida tion in the isolated working rat heart. All hearts were perfused with Krebs-Henseleit buffer containing 11 mM [5-H-3,C-14(U)]glucose, 100 mu U/mL insulin, and 3% albumin. In the presence of 0.4 mM palmitate and 1.25 mM free Ca2+, isoproterenol (3x10(-8) M) increased the heart rat e x peak systolic pressure product from 27+/-1 to 43+/-1 mmHg . beats . min(-1). 10(-3) (1 mmHg=133.3 Pa). This was accompanied by an increa se in glycolytic rates from 3564+/-231 to 7775+/-475 nmol . g(-1) dry weight . min(-1) and an increase in glucose oxidation from 930+/-72 to 2591+/-239 nmol . g(-1) dry weight . min(-1). Addition of PGE(2) (10( -9) M) did not affect the isoproterenol stimulation of glycolysis, but caused a further increase in glucose oxidation (to 3863+/-495 nmol . g(-1) dry weight . min(-1)). In the absence of isoproterenol, 10(-9) M PGE(2) had no effect on either glycolysis or glucose oxidation. When perfusate [Ca2+] was raised to 2.5 mM, a significant increase in glyco lysis was seen in control hearts (from 3564+/-231 to 5679+/-374 nmol . g(-1) dry weight . min(-1)). The effects of isoproterenol and PGE(2) on glucose metabolism remained, although the synergistic effects of PG E(2) on glucose oxidation were less dramatic. When 1.2 mM palmitate wa s present in hearts perfused with 2.5 mM Ca2+, a decrease was seen in both glycolysis (from 5679+/-374 to 3027+/-346 nmol . g(-1) dry weight . min(-1)) and glucose oxidation (from 1056+/-170 to 221+/-29 nmol . g(-1) dry weight . min(-1)). Even at this high concentration of fatty acid, isoproterenol stimulated glucose oxidation (from 221+/-29 to 859 +/-69 nmol . g(-1) dry weight . min(-1)), and addition of PGE(2) resul ted in a significant further increase (1021+/-139 nmol . g(-1) dry wei ght . min(-1)). These data demonstrate that concentrations of PGE(2) t hat bind to the high affinity cardiac PGE(2) receptor have no effect o n glucose metabolism in the absence of beta-agonists. In the presence of isoproterenol, which dramatically stimulates both glycolysis and gl ucose oxidation, PGE(2) has a synergistic effect on glucose oxidation at lower fatty acid concentrations. These findings suggest that PGE(2) receptors in the heart function to potentiate rather than decrease be ta-adrenergic stimulation of glucose metabolism.