Substance P and Neurotensin: Discovery, Isolation, Chemical Characterization and Physiological Studies

Abstract

During the course of work directed towards the purification of a corticotro-pin-releasing factor, two other biological active substances were discovered in bovine hypothalamic extracts: one a sialogogic peptide, the other a vaso-active substance easily separated from the sialogogic agent by ion-exchange chromotography. The sialogogic peptide was subsequently characterized as substance P (SP); the other substance, also a peptide, was named neurotensin (NT). These peptides were isolated, their amino acid sequences determined (substance P; arg-pro-lys-pro-gln-gln-phe-phe-gly-leu-met-NH2; neurotensin: < glu-leu-tyr-glu-asn-lys-pro-arg-arg-pro-tyr-ile-leu-OH), synthetic material prepared, and radioimmunoassays developed. Subsequent studies from many laboratories have yielded much information relevant to the physiological roles of these peptides. In addition to its uneven distribution throughout the CNS, SP is also present in the peripheral nervous system. Data is presented on its distribution in sympathetic ganglia and its depletion by pretreatment with capsaicin. Release of immunoreactive substance P (I-SP) has been demonstrated in vivo from mammalian spinal cord after activation of nociceptive afferents. Neurotensin is also unevenly distributed throughout the CNS and is present in the GI tract. Neurotensin containing cells have been demonstrated scattered throughout the small intestinal epithelium of every mammalian and avian species. The concentration of immunoreactive NT has been measured to increase in hepatic portal vein plasma after infusing a micellar solution of lipid through the small intestine of rats. Neurotensin has been demonstrated to be present in a cell line derived from a rat medullary thyroid carcinoma permitting studies on the regulation of neurotensin release from these cells in culture.