Structure, function, and phylogeny of [Arg8]vasotocinreceptors from teleost fish and toad.

[Arg8]Vasotocin (AVT) is considered to be the mostprimitive known vertebrate neurohypophyseal peptide of the vasopressin/oxytocinhormone family and may thus be ancestral to all the other vertebrate peptidehormones. The molecular evolution of the corresponding receptor family has nowbeen studied by cloning an AVT receptor, consisting of 435 amino acid residues,from the teleost fish, the white sucker Catostomus commersoni. Frog oocytesinjected with the AVT receptor-encoding cRNA respond to the application of AVT,but not to its structural and functional counterpart isotocin, by an inductionof membrane chloride currents indicating the coupling of the AVT receptor to theinositol phosphate/calcium pathway. The pharmacological properties of theexpressed AVT receptor show that it represents, or is closely related to, anancestral nonapeptide receptor: oxytocin, aspargtocin, mesotocin, andvasopressin activated the receptor, but other members of thevasopressin/oxytocin family tested showed little or no potency; antagonists ofthe mammalian vasopressin V1 and oxytocin receptors blocked the AVT response.Comparison of AVT receptor sequences spanning transmembrane domains two to five,deduced by cloning cDNAs from the Pacific salmon Oncorhynchus kisutch, thecave-dwelling fish Astyanax fasciatus, and the anuran Xenopus laevis, with thoseof their mammalian counterparts emphasizes amino acid residues that are involvedin hormone binding. The presence of a 5.0-kb transcript in various teleosttissues (pituitary, liver, gills, swim bladder, and lateral line) points to aphysiological role for the fish AVT receptor in metabolic, osmoregulatory, andsensory processes.