In vitro and in vivo biological activities of PG-KII, a novel kassinin-like peptide from the skin of the Australian frog, Pseudophryne güntheri.

We compared the in vitro and in vivo biological activities of PG-KII (pGlu-Pro-Asn-Pro-Asp-Glu-Phe-Val-Gly-Leu-Met-NH2), a new peptide belonging to the tachykinin family, related to kassinin, isolated and sequenced from extracts of the skin of the Australian myobatrachid frog Pseudophryne güntheri, with those of the well-known tachykinins [substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and kassinin (KASS)] to study its pharmacological and receptor profile. PG-KII always proved inactive in the in vitro and in vivo (gastric emptying) NK2 bioassays. It resulted equipotent to SP and more potent than KASS, NKA, and NKB in all in vitro smooth muscle preparations preferentially activated by the NK1-selective agonists. On an in vivo NK3 receptor-mediated function, gastric acid secretion, PG KII had a potency similar to that of NKB. In contracting guinea pig ileum, which contains NK1, NK2, NK3, and also new tachykinin receptor subtypes, PG-KII was more potent than SP, NKB, and NKA. The cholinergic antagonist, atropine, significantly reduced the guinea pig contractile activity of both PG-KII and NKB but not that of SP or NKA. Pretreatment with the NK1 selective antagonist, CP 96,345, and with the NK2-selective antagonist, MEN 10,376, modified neither the in vivo nor the in vitro effects of PG-KII. These findings indicate that PG-KII is neither an NK1 nor an NK2 receptor agonist but has a spectrum of biological actions close to that of the NK3 receptor agonists. PG-KII elicits strong contractile activity in guinea pig ileum. Administered centrally in the rat it regulates inhibition of gastric acid secretion.