Laufer R, Gilon C, Chorev M, Selinger Z
J Med Chem. 1986 Jul;29(7):1284-8. doi: 10.1021/jm00157a029.
Substitution of a single amino acid residue, proline for glycine-9 in [pGlu6]SP6-11, a hexapeptide analogue of substance P, confers on the peptide selective agonist activity toward the SP-P receptor subtype. [pGlu6,Pro9]SP6-11 had 20% and 75% of the activity of [pGlu6]SP6-11 in stimulating, respectively, K+ release from rat parotid slices and contraction of the isolated guinea pig ileum, via the SP-P receptor subtype. In contrast, [pGlu6,Pro9]SP6-11 had substantially reduced activity on SP-E systems such as the hamster urinary bladder and rat duodenum, being about 20-fold less potent than [pGlu6]SP6-11 and 200-670-fold less potent than neurokinin B. In the guinea pig ileum [pGlu6,Pro9]SP6-11 had very low activity on the neuronal tachykinin receptor, being 325 times less potent than [pGlu6]SP6-11 and 1000 times less potent than neurokinin B. Because of its discrimination between the muscular and neuronal receptors in the guinea pig ileum (muscular/neuronal potency ratio = 600), [pGlu6,Pro9]SP6-11 can be used to specifically desensitize the muscular receptor of this tissue. This procedure enables a selective and sensitive bioassay of the neuronal receptor.
将P物质的六肽类似物[pGlu6]SP6 - 11中的单个氨基酸残基甘氨酸 - 9替换为脯氨酸，可赋予该肽对SP - P受体亚型的选择性激动剂活性。[pGlu6,Pro9]SP6 - 11通过SP - P受体亚型刺激大鼠腮腺切片释放K⁺和使离体豚鼠回肠收缩的活性分别为[pGlu6]SP6 - 11的20%和75%。相比之下，[pGlu6,Pro9]SP6 - 11对SP - E系统（如仓鼠膀胱和大鼠十二指肠）的活性大幅降低，其效力比[pGlu6]SP6 - 11低约20倍，比神经激肽B低200 - 670倍。在豚鼠回肠中，[pGlu6,Pro9]SP6 - 11对神经元速激肽受体的活性非常低，其效力比[pGlu6]SP6 - 11低325倍，比神经激肽B低1000倍。由于其在豚鼠回肠中对肌肉和神经元受体的区分（肌肉/神经元效力比 = 600），[pGlu6,Pro9]SP6 - 11可用于特异性地使该组织的肌肉受体脱敏。此方法可实现对神经元受体的选择性和灵敏生物测定。
