Parallel bioassay of PG-SPI, an amphibian acidic SP-like peptide, mammalian basic substance P, and neurokinins A and B on in vitro and in vivo test systems.
In vitro and in vivo test systems were used to compare the biological activities of substance P and the neurokinins A and B with those of a newly isolated substance P-like acidic peptide, PG-SPI (pGlu-Pro-Asn-Pro-Asp-Glu-Phe-Phe-Gly-Leu-Met-NH2). On nearly all the isolated smooth muscle preparations tested, PG-SPI appeared only slightly more potent than SP, but on guinea pig trachea it was 50 times more potent. The in vitro spasmogenic effect of PG-SPI on guinea pig trachea was inhibited by the NK1 receptor antagonist, CP 96,345. In in vivo tests, intracerebroventricularly injected PG-SPI was about 20 times more potent than SP in inhibiting gastric acid secretion and emptying in rats. Tests with antagonists showed that CP 96,345 reduced PG-SPI-induced inhibition of gastric emptying and the NK2 receptor antagonist, MEN 10,376, sharply blocked PG-SPI-induced inhibition of gastric acid secretion. These findings fit poorly into the current classification of tachykinin receptors and suggest that the acidic substance P-like peptide is a valuable tool for studying the functional role of other tachykinin receptor subtypes.
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006224:Cricetinae; D005069:Evaluation Studies as Topic; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000032:analysis* / Q000494:pharmacology; D015287:Neurokinin B / Q000032:analysis*; D009842:Oligopeptides / Q000032:analysis*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011817:Rabbits; D011898:Ranidae; D051381:Rats; D017208:Rats, Wistar; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000032:analysis*
D001713:Biphenyl Compounds; D009842:Oligopeptides; D010446:Peptide Fragments; D018039:Receptors, Tachykinin; C096302:pyroglutamyl-prolyl-asparaginyl-prolyl-aspartyl-glutamyl-phenylalanyl-phenylalanyl-glycyl-leucyl-methioninamide; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D011761:Pyrrolidonecarboxylic Acid; C066892:CP 96345