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SummaryProstacyclin (PGI2) infused intravenously into anaesthetized rabbits inhibited electrically-induced thrombus formation in the carotid artery, increased bleeding time and inhibited ex vivo platelet aggregation induced by ADP or arachidonic acid. The increase in bleeding time and the inhibition of ex vivo platelet aggregation lasted for as long as the infusion of PGI2 was maintained but rapidly disappeared after infusion was stopped.Prostacyclin is a more potent inhibitor of platelet function, in vivo than prostaglandin E1 (PGE1) or prostaglandin D2 (PGD2).The effects of prostacyclin on all parameters studied except blood pressure were potentiated by the concomitant administration of theophylline, a phosphodiesterase inhibitor.

Structure-activity relations of a series of analogues of the two endo­genous morphine-like peptides, leucine-enkephalin and methionine-enkephalin are examined on the basis of ( a ) effects on the mouse vas deferens and the guinea pig ileum and ( b ) affinities for the rat brain opiate receptor. In the mouse vas deferens, metabolism of the peptides by proteolysis is not a major influence on activity. In contrast, however, brain opiate re­ceptor preparations contain an abundance of proteolytic enzymes, the effects of which can be minimized by conducting opiate receptor binding assays at 0 °C and in the presence of bacitracin. The potentiation of biological activity and opiate receptor binding affinity by replacing the Gly 2 residue in the natural enkephalins by d-Ala, is discussed both in terms of increased stability of the Tyr-d-Ala bond to aminopeptidases and of the stabilization of the peptide conform­ation as present in the receptor-peptide complex. The substitution of the Leu 5 - or Met 5 -residue by the corresponding d-amino acid contributes little to proteolytic stability, which emphasizes that the predominating site at which metabolism occurs is the Tyr 1 -Gly 2 bond. Of the analogues described, [d-Ala 2 , d-Leu 5 ]-enkephalin is the most active peptide in the three assay systems, the mouse vas deferens, the guinea pig ileum and the rat brain opiate receptor preparations. Substitutions by the respective d-amino acids d-Tyr and d-Phe at positions 1 and 4 reduce both the potency and binding affinity and emphasize the importance of stereochemical acceptability at these positions. The promotion of receptor binding by d-amino acids is examined, particularly with respect to implied peptide conformations. The experi­mental data have been analysed for the relative influence of metabolic and conformational factors.

Summary1. Hamster stomach strips in vitro are useful test preparations for the assay of prostaglandins E and F in the nanogram concentration range. Threeminute cycles can be used for long periods without spontaneous contractions or significant base-line instability.2. The mean percentage error and the precision index of six 4-point assays of prostaglandin E2 were 7-8 and 0057, respectively.3. The relative sensitivity to different prostaglandins was E2/E-'1, E2/Fla-65and E2/Av-400. 4. These preparations were relatively insensitive to 5-hydroxytryptamine (prostaglandin E2/5-HT-20,000) and histamine (prostaglandin E2/ histamine -200).5. These results suggest that the hamster stomach preparation can be used to differentiate between 5-hydroxytryptamine and prostaglandins.