Effects of some naturally occurring prostaglandins of the D-, E-, and I-type and synthetic analogues on adenylate cyclase of human fat cell ghosts

Abstract

The effects of various prostaglandins originating from arachidonic acid (prostaglandin E2, D2, I2) as well as of methylated analogues of prostaglandin E2 (16,16-dimethyl prostaglandin E2 and 15-S-methyl prostaglandin E2) on the human fat cell adenylate cyclase were studied. In addition, the stable breakdown product of prostaglandin I2, prostaglandin 6-keto-F1-alpha, was tested for activity. Prostaglandin E2 and its methylated analogues as well as prostaglandin D2 and I2 were active stimulators of the human fat cell enzyme. The stable breakdown product of prostaglandin I2 (prostaglandin 6-keto-F1-alpha) which is biologically inactive had no stimulatory effects, suggesting that stimulation of the human fat cell function. The stimulatory action of prostaglandin D2 is consistent with the elevation of cAMP-levels induced by this compound in intact fat cells. It is concluded that the stimulatory effects of prostaglandins on the human fat cell adenylate cyclase are related to their stimulatory effects upon lipolysis.

Regulation of endothelial cell cyclic nucleotide metabolism by prostacyclin.

“…Since PGI2 is a potent stimulator of adenylate cyclase in a variety of cell types (10)(11)(12) we felt it was important to assess the influence of PGI2 on endothelial cell adenylate cyclase as well. PGI2 proved to be a potent stimulator of endothelial cell cyclic AMP accumulation when the cyclic AMP phosphodiesterase was inhibited.…”

“…Vascuilar tissue and especially vascular endothelium are rich sources of PGI2 synthetase activity (5-7), and the relationship(s) between the synthesis of the antiaggregatory PGI2 by vascular elements and the synthesis of the proaggregatory molecule thromboxane A2 by platelets have been widely discussed (3,4,8,9). PGI2 is a potent stimulator of platelet adenylate cyclase (3,4), and elevates cyclic AMP levels in ctiltured human foreskin fibroblasts (10), human fat cell ghosts (11), and several clonal cell lines of central nervous system origin (12). PGI2 also elevates cyclic AMP levels in arterial rings (13), but no experiments on the effect of PGI2 on cyclic AMP levels in endothelial cells have been reported to date.…”

Eighth Gaddum Memorial Lecture University of London Institute of Education December 1980: Biological Importance of Prostacyclin

“…These include cultured human fibroblasts (Gorman, Hamilton & Hopkins, 1979), human fat cell ghosts (Kather & Simon, 1979), guinea-pig lung homogenates (Macdermot & Barnes, 1980) and polymorphonuclear leukocytes (Boxer, Allen, Schmidt, Yoder & Baehner, 1980). Thus, there is the possibility that in these cells an interaction with the thromboxane system could lead to a similar regulation of cell behaviour to that observed in platelets, suggesting that the PGI2/TXA2 system has a wider biological significance.…”

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“…Prostacyclin increases cyclic AMP levels in cells other than platelets. These include cultured human fibroblasts (Gorman, Hamilton & Hopkins, 1979), human fat cell ghosts (Kather & Simon, 1979), guinea-pig lung homogenates (Macdermot & Barnes, 1980) and polymorphonuclear leukocytes (Boxer, Allen, Schmidt, Yoder & Baehner, 1980). Thus, there is the possibility that in these cells an interaction with the thromboxane system could lead to a similar regulation of cell behaviour to that observed in platelets, suggesting that the PGI2/TXA2 system has a wider biological significance.…”