title: Non-peptide antagonists, CP-96,345 and RP 67580, distinguish species variants in tachykinin NK1 receptors.
abstract: 1. The potency of the non-peptide antagonists CP-96,345 and RP 67580 on NK1 receptor-stimulated [3H]-inositol phosphate accumulation in cell lines or tissue from three different species has been examined. 2. We have used: UC11 cells, derived from a human astrocytoma, and rat LRM55 glial cells, both of which express large numbers of functional NK1 receptors, and the well characterized guinea-pig ileum which expresses both NK1 and NK3 receptors. 3. RP 67580 has an approximately 25 fold lower affinity for NK1 receptors in human UC11 cells (Kd = 194 nM) than in rat LRM55 cells (Kd = 7.9 nM), in contrast CP-96,345 has an approximately 200 fold lower affinity in rat LRM55 cells (Kd = 210 nM) relative to human UC11 cells (Kd = 0.99 nM). The pharmacological profile of CP-96,345 and RP 67580 in guinea-pig ileum was similar to that observed in human UC11 cells. 4. In conclusion, we have demonstrated that previously reported species differences in binding affinities for the non-peptide NK1 antagonists, CP-96,345 and RP 67580, are also observed in inhibition of NK1 receptor stimulated hydrolysis of inositol phospholipids.
authors.affiliation: University Department of Pharmacology, Oxford.
authors.forename: A J
authors.initials: AJ
authors.lastname: Barr
authors.forename: S P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D000818:Animals; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D006868:Hydrolysis; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism*; D054833:Isoindoles; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D015287:Neurokinin B / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D001713:Biphenyl Compounds; D007211:Indoles; D007295:Inositol Phosphates; D054833:Isoindoles; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; C033611:substance P, methyl ester-; D015287:Neurokinin B; D002217:Carbachol; C066892:CP 96345