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Non‐peptide antagonists, CP‐96,345 and RP 67580, distinguish species variants in tachykinin NK 1 receptors
Author(s) -
Barr A.J.,
Watson S.P.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13466.x
Subject(s) - receptor , tachykinin receptor , biology , inositol phosphate , inositol , medicine , endocrinology , substance p , microbiology and biotechnology , neuropeptide , biochemistry
1 The potency of the non‐peptide antagonists CP‐96,345 and RP 67580 on NK 1 receptor‐stimulated [ 3 H]‐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 NK 1 receptors, and the well characterized guinea‐pig ileum which expresses both NK 1 and NK 3 receptors. 3 RP 67580 has an ∼25 fold lower affinity for NK 1 receptors in human UC11 cells ( K d = 194 n m ) than in rat LRM55 cells ( K d = 7.9 n m ), in contrast CP‐96,345 has an ∼200 fold lower affinity in rat LRM55 cells ( K d = 210 n m ) relative to human UC11 cells ( K d = 0.99 n m ). 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 NK 1 antagonists, CP‐96,345 and RP 67580, are also observed in inhibition of NK 1 receptor stimulated hydrolysis of inositol phospholipids.