A new selective bioassay for tachykinin NK 3 receptors based on inositol monophosphate accumulation in the guinea pig ileum

Abstract

The selective agonists of tachykinin NK 1, NK 2 and NK 3 receptors, respectively [Pro 9]substance P, [Lys 5,MeLeu 9,Nle 10]neurokinin A-(4–10) and senktide, stimulated phosphoinositide breakdown in slices of the guinea pig ileum. This was also the case with septide which has recently been found to act on a new type tachykinin receptors in this issue. The NK 1, NK 2 and septide-evoked responses were completely antagonized in the combined presence of (±)-CP-96,345 and MEN 10,376 which are potent and selective antagonists of tachykinin NK 1 and NK 2 receptors respectively in the guinea pig ileum. Like senktide, other available NK 3 receptor agonists, such as [MePhe 7]neurokinin B, [MeVal 7]neurokinin B, [Pro 7]neurokinin B and and DiMe-C7, stimulated phosphoinositide hydrolysis in either the absence or combined presence of (±)-CP-96,345 and MEN 10,376, although senktide was the most potent. Therefore, following the blockade of tachykinin NK 1, NK 2 and septide-sensitive receptors, the accumulation of inositol monophosphate appears to be a valuable, rapid and sensitive bioassay for determining the activity of NK 3 receptor agonists and putative NK 3 receptor antagonists.