Peter W. Ramwell

THE BIOLOGICAL SIGNIFICANCE OF THE PROSTAGLANDINS

The b i o l o g i c a l s i g n i f i c a n c e of p r o s t a g l a n d i n s a t t h e t i m e of t h i s meet ing l i e s p r i m a r i l y i n t h e i r u b i q u i t y , h i g h potency and r emarkab le d i v e r s i t y o f pha rmaco log ica l e f f e c t s . The promise of t h e s e compounds l ies i n three a r e a s f n a m e l y c e l l r e g u l a t i o n , p a t h o l o g y and t h e r a p e u t i c s .

RELATION OF CYCLIC AMP TO THE RELEASE AND ACTIONS OF PROSTAGLANDINS

In studying the biological effects of the prostaglandins, one is impressed by the ubiquity of their distribution and their unparalleled ability to modify hormone action, an effect now known to correlate with changes in cyclic AMP levels in many different cell types. Prostaglandins themselves are known to stimulate accumulation of cyclic AMP in many different tissues, while in other tissues inhibitory effects of prostaglandins on certain hormone-induced cyclic AMP-mediated responses have been 24 A regulatory role for endogenous prostaglandins has been postulated since, in general, both quantitative and qualitative changes in the cellular efflux of prostaglandins have been detected following hormonal stimulation of tissues.

Prostaglandin E1 in Platelet Harvesting: An in vitro Study

Prostaglandin E1 (10-8 to 1O-7 molar) is effective in improving the preparation of human platelet concentrates from plasma rich in platelets and from whole blood. A procedure has been developed for the use by blood banks, on a trial basis.

Prostaglandin E2: Effects on aggregation, shape change and cyclic AMP of rat platelets

Abstract PGE2 inhibits intracellular cyclic AMP accumulation induced by PGE1 in rat platelets. PGE2 also counteracts PGE1-inhibition of both platelet aggregation and shape change. However, in the presence of theophylline, PGE2 acts like PGE1 in inhibiting aggregation. The mechanism of interaction of the two closely related prostaglandins is discussed.

Correlation of prostaglandin E1 receptor binding with evoked uterine contraction: Modification by disulfide reduction

Abstract Both reversible (K3 = 0.72 × 108 1/mole) and irreversible (K = 0.62 × 108 1/mole) binding of PGE1-H3 was observed in rat uterus and was correlated with induced myometrial contraction. Each binding process consisted of a fast and slow component. In the binding that occurred prior to the onset of the uterine response (≤60 sec), the fast reversible component ( T 1 2 ∼ 5 sec ) represented ∼ 80%, the slow reversible component ( T 1 2 ∼ 27 sec ) represented 15% and the remaining 5% was associated with the combined fast and slow irreversible components ( T 1 2 ∼ 24 and 155 sec respectively). Reversible and irreversible binding were PGE1-H3 concentration-dependent, sensitive to competition by PGE1 and modified by inhibitors of prostaglandin-induced uterine contraction. This modification was reflected as a significant reduction in the velocity of PGE1-H3 binding. Only the above characteristics associated with reversible PGE1 binding fully satistified the physiological requirements of receptor interaction. In addition, a critical role for disulfide groups in the receptor binding site was indicated.