Relative activities of substance P-related peptides in the guinea-pig ileum and rat parotid gland, in vitro.
The relative potencies of a series of substance P analogues have been determined for spasmogenic activity in the guinea-pig ileum in vitro and for the release of 86Rb and alpha-amylase activity from rat parotid gland slices in vitro. Equipotent molar ratios (EMR), relative to substance P, were determined for all the compounds. In the rat parotid gland, EC50 values for amylase release were, on average, 35.5 times greater than those for 86Rb release. Analysis of Hill plots suggests that spare receptors exist for 86Rb release but not for amylase release and it is suggested that the stimulus-response coupling for amylase release may be less efficient than that for 86Rb release. In the parotid gland, the octapeptide and [less than Glu6]-hexapeptide C-terminal fragments of substance P were less active than substance P itself, whereas in the ileum, the octapeptide was as active as substance P. Substitutions at the Phe7 or Phe8 positions in general reduced activity relative to substance P. This effect was particularly apparent in C-terminal hexapeptide analogues. Substitutions at the Phe7 and Phe8 positions in C-terminal hexapeptide analogues produced a greater reduction in activity in the parotid gland than in the ileum. The most marked difference was observed with eledoisin-related peptide for which the ratio of EMRs for ileum and 86Rb release was 18.1. The unsubstituted C-terminal octapeptide fragment similarly showed a discrepancy between the two assay systems (EMR ratio, ileum: 86Rb release = 7.75). It is suggested that the results may indicate the presence of sub-populations of 'substance P receptors' which are represented at least in different proportions in the two tissues studied, although alternative explanations such as differences in metabolism of agonists are possible.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010306:Parotid Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis; D018040:Receptors, Neurokinin-1; D012413:Rubidium / Q000378:metabolism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D018040:Receptors, Neurokinin-1; D013373:Substance P; D000681:Amylases; D012413:Rubidium; D002118:Calcium