Neurotensin.

Abstract

Over the last decade there has been a great expansion of knowledge in the field of peptide hormones. Several of these peptides have been discovered by serendipity during the isolation of other peptide hormones, for example pancreatic polypeptide which was found during the purification of chicken insulin, and glucose-dependent insulin-releasing polypeptide, found as a contaminant of cholecystokinin. Neurotensin was discovered in a similar way during the isolation of substance P from bovine hypothalamus, when it was noticed that certain chromatographic fractions of the tissue extract had the ability to cause marked vasodilatation in the exposed cutaneous areas of anaesthetised rats and, in larger doses, to cause severe cyanosis. Subsequently, it was found that this vasodilatation was associated with a transient hypotension. The active constituent was isolated by Carraway and Leeman in 1973 and given the name neurotensin because of its presence in neural tissue and its ability to affect blood pressure. After its purification, neurotensin was found to contain 13 amino-acids and to have a molecular weight of 1674. The amino-acid sequence (Fig.) was deduced from analysis of fragments generated by several proteolytic enzymes, as well as from information obtained on the intact peptide (Carraway and Leeman, 1975a). It has been synthesised using the Merrifield solid phase procedure and the resultant peptide appeared to be identical with the native form, using multiple chemical and biological criteria (Carraway and Leeman, 1975b). There is still some uncertainty about the glutamic acid in position 4, as this may be formed from glutamine during the extraction procedure. The amino-acid sequence of neurotensin suggests a distant relationship with vasopressin and