Parallel Bioassay of Pg-spi, An Amphibian Acidic Sp-like Peptide, Mammalian Basic Substance-p, and Neurokinin-a and Neurokinin-b On In-vitro and In-vivo Test Systems

In vitro and in vive 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.