Structural requirements of amino acids and related compounds for stimulation of receptors in crayfish walking leg

Summary Previous recordings from single afferent neurons in the walking legs of the crayfish demonstrated the presence of amino acid sensitivity; several characteristics of this extracellularly recorded impulse discharge, such as responses to mixtures of effective amino acids and cross adaptation experiments, indicate that all such units represent a single type of receptor. Here the effectiveness of more than 100 systematically varying amino acids and analog substances were tested in eliciting a response of the cell. Molecules lacking the amino or carboxyl group were found to be ineffective. The amino group must be unsubstituted and bear an ionic charge; modifications of the carboxyl group, including removal of charge, are tolerated with some loss of effectiveness. Replacement of the-hydrogen by a methyl group reduced effectiveness by about 1 decade. Amino acids not in the L configuration, or the amino group of which was not in the position, were still less effective. The affinity of the amino acids for the receptor was related to the number of C atoms in the side chain, with a maximum at 3. Molecules with voluminous, hydrophobic or negatively charged side chains had little effect. For high effectiveness, the side chain should be short and bear a hydrophilic group, but there is relatively little restriction on its chemical properties. These findings suggest the presence of three subunits in the receptive area. One of the proposed subunits would be involved in ionic binding to the amino group and the two others, in the formation of hydrogen bridges to the carboxyl group and the side chain. Their orientation with respect to one another would be expected to meet certain steric requirements.