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Four structural analogues of oxytocin were investigated with regard to their oxytocic, milkejecting, pressor and diuretic/antidiuretic effects. In three of them the isoleucyl group of oxytocin was replaced by a phenylalanyl, leucyl, or valyl residue; in the fourth the asparaginyl group was replaced by a glutaminyl residue. Synthetic oxytocin and the international standard pituitary (posterior lobe) powder were used for comparison. Although the analogues showed marked differences in their oxytocic effects, there was a fairly good agreement between the results obtained on the isolated rat uterus and the blood pressure of the chicken for each polypeptide. The milk-ejection pressure test gave much higher values throughout. The pressor and antidiuretic activities of the four analogues showed no obvious correlation with the values obtained in the other tests. The valyl and the leucyl analogues also had a diuretic effect. The phenylalanyl analogue was remarkable for the close correspondence between its oxytocic and antidiuretic effects: practically identical values were obtained for the potency, whether measured on the rat uterus in vitro, the blood pressure in the chicken, the cat uterus in situ or water diuresis in the rat. The leucyl analogue showed an oxytocic activity on the cat uterus in situ or the rabbit mammary gland roughly 7 to 9 times as high as that measured by means of the conventional bioassay methods, such as the blood pressure of the chicken or the rat uterus in vitro. The glutaminyl analogue, the weakest of the whole series, had only a modest effect on the mammary gland. The valyl analogue was the most interesting of the new polypeptides. Its oxytocic action on the cat uterus in situ and its milk-ejecting effect were greater than that of synthetic oxytocin, whereas its antidiuretic and pressor effects were less. In cats and rats, the uterine effect was stronger in situ than in vitro. There were also distinct species differences between cats, rabbits, and rats in their sensitivity to valyl-oxytocin.

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Various reports suggest that 5-hydroxytryptamine (5HT) can cause bronchoconstriction. Thus, Reid and Rand (1952) (Gaddum, Hebb, Silver, and Swan, 1953) and guinea-pig (Bhattacharya, 1955). A constrictor effect of 5HT has also been noted in the tracheal chain of the guineapig (Freyburger et al., 1952) and cat (Sinha and West, 1953). Furthermore, 5HT administered as an aerosol causes dyspnoea in the guinea-pig, resembling that produced by histamine or acetylcholine (Herxheimer, 1953a(Herxheimer, , 1953b(Herxheimer, , and 1955.As yet, the effect of 5HT on tidal air has not been investigated in the intact and spinal animal. It therefore seemed of interest to make such an investigation with a view to obtaining further information on the mode of action. Another purpose of the study was to investigate whether agents found to be potent antagonists of 5HT in isolated organs in vitro also antagonize the bronchoconstriction induced by SHT in vivo. METHODSCats were anaesthetized with a mixture of chloralose (0.05 g./kg.) and urethane (0.5 g./kg.) administered subcutaneously. In the course of some experiments first the vagi were cut and later the spinal cord was sectioned at C 1. Guinea-pigs were anaesthetized by intraperitoneal administration of urethane (1.2 g. /kg.). Spinal cats and guinea-pigs were also used, the operation being conducted under ether anaesthesia.