Isolation and identification of pharmacologically active amino acids in skin and their structure‐activity relationship on the guinea‐pig ileum

Abstract

Summary1. Aqueous extracts of stratum corneum were found to cause histamine-like contractions of the guinea-pig ileum which were not antagonized by mepyramine, atropine or bromolysergic acid diethylamide. 2. The compounds responsible for this contraction were isolated by chromatography and shown to be common amino acids, particularly L-serine and L-alanine which occur in abundance in the stratum corneum. 3. Amino acid analogues were assayed on the guinea-pig ileum against alanine as standard. With the exception of y-amino butyric acid and L-alanine benzyl ester all analogues which had appreciable activity gave dose-response curves parallel to L-alanine. 4. The response to L-alanine benzyl ester was abolished by mepyramine and this analogue appears to be a partial agonist on the histamine receptor. 5. The effects of substitution on the equipotent molar ratios of amino acid analogues indicate that all four chemical groups attached to the a-carbon of L-alanine interact with the receptor. 6. Our results suggest that the guinea-pig ileum contains an L-a-amino acid receptor.

Effects of homopantothenic acid on intestinal smooth muscles.

“…It is interesting that unlike GABA, HOPA has only a myotropic action, although it is one of the GABA derivatives, In agreement with results by previous investigators (Hobbiger 1958;Inouye et al 1960; Lewis et al 1972; Krantis et al 1980), the relaxation and contraction of the guinea-pig ileum in response to GABA is absolished by TTX in the present study. That the mode of action of HOPA on smooth muscle differs from that of GABA might be due to its pantoyl residue of HOPA.…”

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

“…Our experiments on the guinea-pig uterus broadly confirm those of Lewis et al (1972) on the ileum, in that a wide range of amino acids, but not all, can strongly stimulate smooth muscle when added in concentrations from 2 to 10 mM. Although it is difficult to make exact comparisons between the two investigations, there may be some significant differences ,,,,,,,,,,,,,,,,,,,,,. Such considerations are relevant to the comparison with the effects of amino acids on central neurones.…”

“…Amino acids may stimulate smooth muscle (Jones, 1962;Klingenberg, 1966;Lewis, McMartin, Rosenthal & Yates, 1972). Among these, the only extensive study of amino acids in general was that of Lewis et al (1972), who were concerned to identify the nonhistamine active substances in the stratum comeum of human skin, and to define the receptors on which the substances acted; these authors used the guinea-pig ileum as their test object.…”

“…Among these, the only extensive study of amino acids in general was that of Lewis et al (1972), who were concerned to identify the nonhistamine active substances in the stratum comeum of human skin, and to define the receptors on which the substances acted; these authors used the guinea-pig ileum as their test object. We, however, wished to study a possible parallelism between the actions of amino acids in stimulating smooth muscle, and in depolarizing cells in the central nervous system (CNS).…”

GABAA‐receptor‐mediated inhibition of the delayed increase in intragastric pressure to stimulation of vagal afferent fibres in cats

“…In some experiments it has been found to stimulate the smooth muscle indirectly by exciting cholinergic neurones and, in areas of intestine where relaxations can be recorded easily, GABA stimulates enteric inhibitory neurones (Hobbiger, 1958;Inouye et al, 1960;Lewis et al, 1972;Krantis et al, 1980). GABA also depresses the contractions of the small intestine caused by stimulation of enteric cholinergic neurones (Ong & Kerr, 1983).…”