Structure-activity relationship of neuropeptide gamma derived from mammalian and fish

This study of relationship between structure and biologic activity was performed using five neuropeptide gammas [NPgamma; mammalian-NPgamma (M-NPgamma), trout-NPgamma (T-NPgamma), goldfish-NPgamma (G-NPgamma), bowfin-NPgamma (B-NPgamma), and shark-NPgamma (S-NPgamma)]. Circular dichroism (CD) spectra showed that all peptides took random structure in buffer solution. In neutral and acidic liposomes, M-NPgamma, T-NPgamma, B-NPgamma, and S-NPgamma still adopted random structure, while G-NPgamma had an alpha-helical structure. The biologic activity of NPgammas has been estimated by their effects on the intestinal motility and arterial relaxation. The intestinal motility was investigated with rat duodenum (RD), carp intestine (CI), and guinea-pig ileum (GPI). The arterial relaxing effect was tested with guinea-pig aorta (GPA) and rat mesenteric artery (RMA). In RD, the order of potency compared with the EC50 value was M-NPgamma >> S-NPgamma >> B-NPgamma >> G-NPgamma >> T-NPgamma. G-NPgamma was the most contractile agent in CI. S-NPgamma was the most contractile agent in GPI. Using an arterial relaxing test, the order of potency was G-NPgamma >> T-NPgamma >> B-NPgamma >> S-NPgamma >> M-NPgamma in GPA, and all NPgammas remarkably reduced relaxing activity in RMA. Despite their structural similarities to NPgammas, G-NPgamma has high affinity to tachykinin receptor-binding sites in GPA and CI, indicating an alpha-helical structure may have a critical role for receptor binding. However, an alpha-helical structure does not play a critical role in recognizing receptor-binding sites in RD and GPI.