A new selective bioassay for tachykinin NK3 receptors based on inositol monophosphate accumulation in the guinea pig ileum.
The selective agonists of tachykinin NK1, NK2 and NK3 receptors, respectively [Pro9]substance P, [Lys5,MeLeu9,Nle10]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 of tachykinin receptors in this tissue. The NK1, NK2 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 NK1 and NK2 receptors respectively in the guinea pig ileum. Like senktide, other available NK3 receptor agonists, such as [MePhe7]neurokinin B, [MeVal7]neurokinin B, [Pro7]neurokinin B 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 NK1, NK2 and septide-sensitive receptors, the accumulation of inositol monophosphate appears to be a valuable, rapid and sensitive bioassay for determining the activity of NK3 receptor agonists and putative NK3 receptor antagonists.
Petitet
F
F
Collège de France, Chaire de Neuropharmacologie, INSERM U 114, Paris.
Saffroy
M
M
Torrens
Y
Y
Glowinski
J
J
Beaujouan
J C
JC
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013268:Stimulation, Chemical; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D007295:Inositol Phosphates; D010446:Peptide Fragments; D010716:Phosphatidylinositols; D010743:Phospholipids; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C067285:substance P, Pro(9)-; C054724:senktide; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D015288:Neurokinin A; C056408:neurokinin A(4-10); C066892:CP 96345