[pGlu6, Pro9]SP6-11, a selective agonist for the substance P P-receptor subtype
- 1 July 1986
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 29 (7), 1284-1288
- https://doi.org/10.1021/jm00157a029
Abstract
Substitution of a single amino acid residue, proline for glycine-9 in [pGlu6]SP6-11, a hexapeptide analogue of substance P, confers on the tide 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 subtantially reduced activity on SP-E systems such as the hamster urinary bladder an 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 tacykinin 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.This publication has 15 references indexed in Scilit:
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