Isolation, structure and biologic activity of chicken intestinal neurotensin

doi:10.1016/0196-9781(80)90082-0

Peptides

Volume 1, Issue 2, Summer 1980, Pages 167-174

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Abstract

Using a radioimmunoassay towards bovine neurotensin (NT), chicken NT has been purified to homogeneity from extracts of intestine and its amino acid sequence determined to be: <Glu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Pro-Tyr-Ile-Leu-OH. The molecule is identical to the bovine peptide except for the 3 amino acid substitutions located in its NH₂-terminal half and italicized above (His/Tyr; Val/Glu; Ala/Pro). The structure for chicken NT is consistent with earlier immunochemical studies which indicated a COOH-terminal homology with bovine NT [1]. The peptide isolated was shown to be near equipotent with bovine NT in its ability to induce hypotension, hyperglycemia, and cyanosis in the anesthesized rat, underscoring the importance of the COOH-terminal residues in NT for biological activity.

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Changes in expression levels of neurotensin precursor and receptor mRNA in chicken intestinal tissues and liver during late embryonic and early posthatching development
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Citation Excerpt :
Neurotensin (NT) is a tridecapeptide that is distributed widely in the central nervous system and peripheral tissues of vertebrates and has multiple functions as a neurotransmitter and as a circulating hormone (Reinecke, 1985; St-Gelais et al., 2006; Kalafatakis and Triantafyllou, 2011). In the chicken, NT was initially isolated from the intestine (Carraway and Bhatnagar, 1980). Thereafter, NT immunoreactivity was found in the epithelium and nerve fibers of the smooth muscle layers of the gastrointestinal tract (Atoji et al., 1994, 1995), endocrine cells of the thymus (Atoji et al., 1996), and the hypothalamus in the brain (Esposito et al., 1997).
Neurotensin is a tridecapeptide that has multiple functions as a neurotransmitter and as a circulating hormone. Neurotensin and its related peptide, LANT6, have been isolated in the chicken, but the mRNA encoding these peptides has not been identified. In this study, we first cloned the cDNA for the chicken neurotensin precursor mRNA from the duodenum and characterized its primary structure and then investigated tissue expression patterns of neurotensin precursor and receptor mRNA. The cDNA encoded a protein of 495 amino acids that contains the sequences of chicken neurotensin and LANT6 in the C-terminal region. Real-time PCR analysis showed that the neurotensin precursor mRNA is preferentially expressed in intestinal tissues, such as the duodenum, jejunum, ileum, and colon/rectum, with temporal increases during the hatching period. The expression levels of neurotensin receptor 1 mRNA were relatively higher during the late embryonic period compared with the posthatching period in the duodenum and jejunum, whereas the expression levels were higher in the colon/rectum during the posthatching period. In the liver, the expression levels of neurotensin receptor 1 were markedly increased during the early posthatching period. These results suggest that chicken neurotensin is involved in the regulation of gastrointestinal and hepatic functions, especially during the hatching period.
Neurotensin and cholecystokinin contract gallbladder circular muscle in chickens
2013, Poultry Science
Citation Excerpt :
Contractions were recorded via force transducers that were connected to a 4-channel polygraph (model 79-D, Grass Instruments, Quincy, MA). Avian NT has been isolated from the intestine of chickens and has a sequence similar to bovine NT (Carraway and Leeman, 1973) except for the substitution of His3, Val4, and Ala7 for Tyr3, Glu4, and Pro7(Carraway and Bhatnagar, 1980). The biologically active carboxy-terminus of the peptide is common to both species.
The contractile effects of neurotensin (NT) and cholecystokinin octapeptide (CCK-8) on isolated circular smooth muscle strips of chicken gallbladder were investigated. The NT (0.25–300 nM) produced concentration-dependent contractions on smooth muscle with an EC₅₀ of 8.5 nM (95% confidence limits = 5.3–13.6 nM). In comparison, CCK-8 produced concentration-dependent contractions with an EC₅₀ of 13 nM (95% confidence limits of 9–20 nM). There were no statistical differences in contractile responses when comparing NT and CCK-8 at equimolar concentrations. The NT appears to act directly on smooth muscle tissue in the chicken; the contractile responses were not blocked by 10 µM atropine or tetrodotoxin. A portion of the activity is mediated by extracellular calcium as 100 nM nifedipine inhibited 30% of peptide-induced muscle tension. The NT receptor (NTR) type 1 antagonist SR 48692 (0.1 µM) did not significantly reduce NT potency. The contractile effects of CCK-8 remained unaltered in tissues pretreated with atropine, TTX, or nifedipine. The CCK-A antagonist lorglumide, at a concentration of 1 µM, reduced the contractile potency of CCK-8 by one-half. Avian receptors for NT and CCK may differ pharmacologically from their mammalian counterparts, but their contractile actions on the gallbladder resulting in increased biliary output by flow are further evidence of their role in the postprandial regulation of lipid digestion in chickens.
Chapter VI Neurotensin receptors in the central nervous system
2002, Handbook of Chemical Neuroanatomy
This chapter reviews the discovery of NT and briefly discusses its synthesis, degradation, distribution, and biological effects in the CNS. It focuses on the characterization and distribution of NT receptors and of their mRNA in adult and developing mammalian brain. Like many other neuropeptides, the tridecapeptide neurotensin (NT) is a messenger of intercellular communication working as a neurotransmitter or neuromodulator in the brain and as a local hormone in the periphery. Several pharmacological, morphological, and neurochemical data suggest that NT is involved in many physiological processes in the central nervous system (CNS), as well as in the gastrointestinal tract. Both central and peripheral modes of action of NT imply as a first step the recognition of the peptide by a specific receptor located on the plasma membrane of the target cell. The activated ligand-receptor complex then transduces the extracellular signal inside the cell.
Neurotensin elevates hepatic bile acid secretion in chickens by a mechanism requiring an intact enterohepatic circulation
2000, Comparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology
Neurotensin (NT), given intravenously at 10–50 pmol/kg per min to anesthetized female chickens equipped with a bile duct fistula, dose-dependently elevated hepatic bile flow and bile acid output but only when the enterohepatic circulation was maintained by returning the bile to the intestinal lumen. Infusion of NT at 10 and 50 pmol/kg per min increased the average hepatic bile acid output over a 30-min period to 138±11 and 188±13% of control, respectively. During infusion of NT, plasma levels of immunoreactive NT (iNT) increased in time from the basal level (14±1.3 pM) to reach steady state at 30 min. There was a near linear relationship between the dose of NT infused and the increment in plasma iNT. In addition, infusion of NT at 40 pmol/kg min gave a plasma level of iNT (≅88 pM) which was within the range of those observed during duodenal perfusion with lipid (54–300 pM) and near to that measured in hepatic portal blood from fed animals (52±5 pM). Perfusion of duodenum with lipid released endogenous NT and increased the rate of hepatic bile flow. When NT antagonist SR48692 was given, bile flow rate decreased to the basal level. These results suggest that intestinal NT, released by lipid, may participate in the regulation of hepatic bile acid output by a mechanism requiring an intact enterohepatic circulation.
Purification, characterization, and spasmogenic activity of neurotensin from the toad Bufo marinus
1998, Peptides
Neurotensin (NT) was isolated from an extract of the intestine of the cane toad, Bufo marinus and its primary structure established as: pGlu-Ala-Ile-Val-Ser-Lys-Ala-Arg-Arg-Pro-Tyr-Ile-Leu. This amino acid sequence shows five substitutions (Leu² → Ala, Tyr³ → Ile, Glu⁴ → Val, Asn⁵ → Ser, and Pro⁷ → Ala) compared with bovine NT. Synthetic Bufo NT (pD₂ = 8.05 ± 0.28) was equipotent and equally effective as bovine NT (pD₂ = 8.24 ± 0.38) in producing spasmogenic contraction of isolated segments of toad small intestine. However, the maximum response produced by Bufo NT was only 35 ± 2% of that produced by substance P. The potencies, but not the maximum responses, to Bufo and bovine NT were significantly (p < 0.05) attenuated by pre-treatment with atropine but neither parameter was significantly diminished by tetrodotoxin and indomethacin. The data suggest that the action of NT involves interaction with receptors on toad intestinal smooth muscle that recognize the C-terminal region of NT (residues 8–13) that has been fully conserved during evolution of tetrapods. Contractile activity is mediated, at least in part, by release of acetylcholine.

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^☆: This research was supported by National Institute of Health Grants AM 19428 and AM 21271

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Isolation, structure and biologic activity of chicken intestinal neurotensin☆

Abstract

Peptides

J. biol. Chem.

J. biol. Chem.

J. biol. Chem.

J. biol. Chem.

J. biol. Chem.