P.2.065 Does improvement in psychopathologycorrelate with improvement in health related quality of life? Results from the SQUARE study

Abstract

We investigated the ability of the first non-peptide tachykinin NK3-receptor antagonist, SR142801, to antagonize contractions of guinea-pig intestinal tissues induced by the putative selective agonists [MePhe7]NKB and senktide. These agonists produced tetrodotoxin-sensitive responses presumably by acting on neuronal NK3-receptors. Indeed, tetrodotoxin (1 μM) fully prevented the [MePhe7]NKB and senktide elicited contractions in taenia caeci, ileum and its electrically stimulated myenteric plexus longitudinal muscle. SR142801 had no intrinsic agonist activity and dose-dependently antagonized the contractions elicited by [MePhe7]NKB or senktide. Its affinity for tachykinin NK3 receptors (mean apparent pKB, 8.98 ± 0.1 SEM) was not dependent on: the agonist, the different intestinal segments tested and the presence or absence of atropine. SR142801 appears to be a potent tachykinin receptor antagonist, selective for guinea-pig intestinal Nk3-receptors. Our findings also suggest that the cholinergic and non-cholinergic responses elicited by [MePhe7]NKB and senktide in the investigated tissues are mediated by the same neuronal tachykinin NK3 receptor.