Spasmogenic and Potentiating Actions of Some Amino Acids on the Guinea‐pig Myometrium

Abstract

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.

EFFECTS OF N‐BENZYL‐ L‐VALINE ON CONTRACTIONS OF GUINEA‐PIG MYOMETRIUM in vitro

“…In such instances the effect may be either stimulation or inhibition of the contractions, or one of these effects may lead to the other. The concentration of NBV sometimes producing stimulation is less than that of the common amino acids showing a similar effect (Bedwani et al, 1977), but the potentiation of other spasmogens given by low concentrations of those acids was not given by NBV. There may be several possible reasons for the difference between the present results and those of Koroza et a.…”

“…The most potent one was stated to be N-benzylvaline (Na salt), which was claimed to intensify contractions at concentrations of the order of 10-19 M, or to cause spasm at 10-13 M. Since a number of common amino acids at much higher concentrations have recently been shown to stimulate the uterus (Bedwani, Ishizawa, Pickles & Suwankrughasn, 1977) conditions were kept constant. By either means, the bath concentration of NBV was usually within the range 0.5 gM to 1.0 mM.…”

“…Introduction Koroza, Kudrin, Kost & Sagitullin (1969) stated that certain N-substituted amino acids markedly enhanced the contractions of the guinea-pig uterus, when applied in exceedingly low concentrations for periods of 10-15 minutes. The most potent one was stated to be N-benzylvaline (Na salt), which was claimed to intensify contractions at concentrations of the order of 10-19 M, or to cause spasm at 10-13 M. Since a number of common amino acids at much higher concentrations have recently been shown to stimulate the uterus (Bedwani, Ishizawa, Pickles & Suwankrughasn, 1977), and as there are a few simple N-substituted amino acids of pharmacological or physiological interest, it seemed worthwhile to see if the claim by Koroza et al (1969) could be substantiated.…”

“…Methods N-benzyl-L-valine (NBV) with the addition of the equivalent amount of NaHCO3 was dissolved in Krebs-Henseleit solution to give 10 mm stock solutions, which were kept at 4°C until they were diluted for use. Guinea-pig uteri were suspended in Krebs-Henseleit solution as in the experiments of Bedwani et aL (1977), except that animals in oestrus were not avoided; 2 of the 17 animals used appeared to be in this phase. For short-term applications, NBV was applied by injection into the organ bath.…”