Tissue selectivity of substance P alkyl esters: suggesting multiple receptors

Previous studies from this laboratory suggested that two subtypes of substance P receptor may exist, based on the observations that substance P and related peptides did not exhibit complete cross-desensitisation on guinea-pig ileum, and that two distinct rank orders of potency of tachykinins were observed in various test systems. The present study has added support to this hypothesis by extending the screening of tachykinins to further bioassays and by testing novel analogues. In particular, C-terminal alkyl esters of substance P were found to exhibit a high degree of selectivity to one putative receptor subtype. The synthesis of the alkyl esters by esterification of substance P free acid is described.