Urotensin II (UII) is a cyclic peptide initially isolated from the caudal neurosecretory system of teleost fish. Subsequently, UII has been characterized from a frog brain extract, indicating that a gene encoding a UII precursor is also present in the genome of a tetrapod. Here, we report the characterization of the cDNAs encoding frog and human UII precursors and the localization of the corresponding mRNAs. In both frog and human, the UII sequence is located at the C-terminal position of the precursor. Human UII is composed of only 11 amino acid residues, while fish and frog UII possess 12 and 13 amino acid residues, respectively. The cyclic region of UII, which is responsible for the biological activity of the peptide, has been fully conserved from fish to human. Northern blot and dot blot analysis revealed that UII precursor mRNAs are found predominantly in the frog and human spinal cord. In situ hybridization studies showed that the UII precursor gene is actively expressed in motoneurons. The present study demonstrates that UII, which has long been regarded as a peptide exclusively produced by the urophysis of teleost fish, is actually present in the brain of amphibians and mammals. The fact that evolutionary pressure has acted to conserve fully the biologically active sequence of UII suggests that the peptide may exert important physiological functions in humans.

The effects of the instillation of glucose, fat, casein hydrolysate, and HCl into the gastrointestinal tract upon plasma levels of somatostatin-like immunoreactivity (SLI) in the venous effluent of the pancreas, fundus and antrum of the stomach, and in the inferior vena cava (IVC) were determined in normal laparotomized dogs. Fasting SLI levels in the effluent plasma from these sites were significantly greater than IVC levels. The intragastric administration of glucose elicited a prompt and significant rise in SLI levels in pancreatic, fundic and antral venous plasma, and in IVC plasma; intraduodenal glucose elicited smaller increments. After intragastric fat, a smaller, more gradual increase in the pancreatic and fundic effluents was observed, whereas the rise in antral SLI was minute, and IVC SLI did not rise significantly. Intraduodenal fat elicited a prompt increase in the pancreatic and antral vein SLI levels, and a small but significant increase in fundic and IVC plasma which suggests faster release of enteric factors that influence SLI secretion in the pancreas and antrum. Intragastric casein hydrolysate elicited a prompt increase in SLI in both the pancreatic and fundic veins, the latter being marked, but the antral SLI response was small; IVC SLI rose significantly within 15 min. Intragastric HCl provoked a prompt and marked rise in pancreaticoduodenal and antral vein SLI but no increase in fundic vein SLI; IVC SLI levels rose significantly within 20 min. Intraduodenal HCl elicited an even more prompt and marked pancreatic SLI response, and SLI rose significantly in both the fundic and antral venous effluents; IVC SLI also rose more promptly. In dogs with a gastric fistula that prevented intraduodenal entry of HCl, intragastric HCl elicited only a very small and transient rise in pancreaticoduodenal vein SLI, markedly stimulated the antral SLI response, but completely suppressed fundic venous SLI levels. The results indicate that all three nutrients stimulate SLI release from the pancreas and stomach. The greater SLI response to intragastric, as opposed to intraduodenal, glucose suggests that unidentified local factors are of importance. The responses to the intraduodenal instillation of HCl and fat suggest a role of enteric hormones in the release of SLI from the pancreas and fundus and antrum of the stomach. Additionally, there is evidence of direct effects of HCl upon gastric SLI release.