非肽类拮抗剂CP-96,345和RP 67580可区分速激肽NK1受体中的物种变体。

Non-peptide antagonists, CP-96,345 and RP 67580, distinguish species variants in tachykinin NK1 receptors.

Barr A J, Watson S P

University Department of Pharmacology, Oxford.

Br J Pharmacol. 1993 Jan;108(1):223-7. doi: 10.1111/j.1476-5381.1993.tb13466.x.

Abstract

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.

摘要

已检测了非肽类拮抗剂CP - 96,345和RP 67580对来自三种不同物种的细胞系或组织中NK1受体刺激的[3H] - 肌醇磷酸积累的效力。2. 我们使用了：源自人星形细胞瘤的UC11细胞和大鼠LRM55神经胶质细胞，这两种细胞均表达大量功能性NK1受体，以及特征明确的豚鼠回肠，其表达NK1和NK3受体。3. RP 67580对人UC11细胞中NK1受体的亲和力（Kd = 194 nM）比对大鼠LRM55细胞（Kd = 7.9 nM）低约25倍，相比之下，CP - 96,345对大鼠LRM55细胞（Kd = 210 nM）的亲和力相对于人UC11细胞（Kd = 0.99 nM）低约200倍。CP - 96,345和RP 67580在豚鼠回肠中的药理学特征与人UC11细胞中观察到的相似。4. 总之，我们已证明，先前报道的非肽类NK1拮抗剂CP - 96,345和RP 67580在结合亲和力上的物种差异，在抑制NK1受体刺激的肌醇磷脂水解中也可观察到。