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

Abstract

1 . 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 γ-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 α-carbon of l-alanine interact with the receptor. 6 . Our results suggest that the guinea-pig ileum contains an l-α-amino acid receptor.