Biological activity of C-terminal partial sequences of substance P.
Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog, isolated guinea pig ileum, and the isolated rabbit ear vein. The tripeptide and tetrapeptide possessed weak vasodilator properties only but no activity was detected on the other less sensitive preparations. The pentapeptide produced appreciable spasmogenic and vasoactive effects. Sequences of six or more C-terminal amino acids were able to elicity activity at comparable doses to that of the parent endecapeptide; however, the activity did not increase regularly with the chain length. In each assay preparation the octapeptide was the most potent peptide. It was twice as potent as substance P on a molar basis in the guinea pig ileum but the enhancement of activity beyond that of substance P was less pronounced in the vascular preparations.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002855:Chromatography, Thin Layer; D003377:Countercurrent Distribution; D004285:Dogs; D004423:Ear / Q000098:blood supply; D006168:Guinea Pigs; D006614:Hindlimb / Q000098:blood supply; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000032:analysis / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects
D000596:Amino Acids; D010446:Peptide Fragments; D013373:Substance P