[pGlu6,Pro9]SP6-11, a selective agonist for the substance P P-receptor subtype.
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.
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments; D011188:Potassium / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism*
D009842:Oligopeptides; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; C026238:substance P (6-11), pGlu(6)-; D011188:Potassium; D011761:Pyrrolidonecarboxylic Acid