Isolation, biological and chemical characterization, and synthesis of a neurotensin-related hexapeptide from chicken intestine

Abstract

A new biologically active peptide of the neurotensin (NT) family, shown previously to cross-react in a COOH-terminal-directed radioimmunoassay for bovine NT, has been isolated from extracts of chicken intestine and identified as H-Lys-Asn-Pro-Tyr-Ile-Leu-OH, which is identical with the biologically active COOH-terminal half of NT except for the amino acid substitutions Lys/Arg and Asn/Arg. It is proposed that this peptide be referred to as Lys8, Asn9, NT8-13 (LANT-6). Synthetic material prepared with this amino acid sequence using the Merrifield technique was immunochemically, chromatographically, and biologically indistinguishable from the native peptide. In contrast to chicken NT which induced hypotension, hyperglycemia, increased vascular permeability, and cyanosis when injected intravenously into anesthetized rats, synthetic LANT-6 brought about primarily a hypertensive response and had little ability to promote hyperglycemia, increased vascular permeability, and cyanosis. In rats pretreated with the alpha-blocker phentolamine and in adrenalectomized rats, the hypertensive response to LANT-6 was blocked, suggesting that adrenal catecholamines mediated this effect. These findings suggest that LANT-6, a natural variant of NT with a different spectrum of biologic activity, may be a NT-related messenger peptide with a different function(s).