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I Thirty-three amino acids were applied separately in concentrations of 2 to 10 mM to guinea-pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions. 2 Glycine and the straight-chain L-a-amino acids up to norleucine were active (longer ones not tested); D-isomers were less potent or inactive in these concentrations. The co-amino acids yaminobutyric acid (GABA) and 6-aminovaleric, and the a,o-diamino acids L-a, P-diaminopropionic and L-a,y-diaminobutyric were active, whereas others of similar chain-length such as f,-alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido-amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity. 3 The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5-hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful. 4 When some of the acids that were spasmogenic at 2 to 10 mm were applied at sub-spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations. 5 There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.

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Ca-induced contracture and the effect of Na on it were investigated in the K-depolarized longitudinal and circular muscles of guinea pig stomach. In the absence of Na, Ca produced rapid contracture in longitudinal muscle, but slow and S-shaped contracture in circular muscle. The sensitivity to Ca for the contracture was about tenfold higher in longitudinal muscle than in circular muscle. The presence of external Na (7.5-60 mM) inhibited the contracture induced by Ca (0.1 mM) in longitudinal muscle in a dose-dependent manner. In circular muscle, however, Na potentiated the initial speed of contracture induced by Ca (1 mM), and inhibited the height of contracture at 30 min showing maximum inhibition at 15 mM Na. Li instead of Na produced inhibition of Ca contractures in both muscle layers. Na-induced potentiation in circular muscle was markedly depressed by lowering the temperature, and was reduced by a high concentration (1 mM) of ouabain.These observations indicate that the Ca contracture in longitudinal and circular muscles differs and the effect of Na on this contracture may modulate Ca ion movements through the muscle membrane by inhibiting Ca influx in both muscle layers, and initially potentiating it in circular muscle in an ouabain-sensitive process.Ca entry to the smooth muscle is increased by substitution of isotonic sucrose for sodium in frog stomach (BOZLER, 1963), by reducing external Na in guinea pig taenia coli (GoODFORD and HERMANSEN, 1961) and in rabbit aorta (BRIGGS and MELVIN, 1961). These reports indicate that external Na affects Ca fluxes through the smooth muscle membrane. In K-depolarized vascular muscle, BIAMINO and JOHANSSON (1970) proposed that the presence of external Na increased both the initial speed and relaxation of Ca contracture, and they suggested that Na is more important for the removal of Ca from the contractile system than for supply to it. On the contrary, it has been reported that Na, added to the external solution, produced relaxation of sucrose-induced contraction in guinea pig ileum (JUDAH and WILLOUGHBY, 1974) and of Na-free contracture in guinea pig taenia