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

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 gamma-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 alpha-carbon of L-alanine interact with the receptor.6. Our results suggest that the guinea-pig ileum contains an L-alpha-amino acid receptor.