-
Journal of Neurochemistry Jul 2023The neurotensin system spans across the central nervous system, to the enteric nervous system (gut), and the periphery to govern behaviors and physiological responses... (Review)
Review
The neurotensin system spans across the central nervous system, to the enteric nervous system (gut), and the periphery to govern behaviors and physiological responses that tune energy balance to maintain homeostasis. Neurotensin transmission is not only modulated by metabolic signals, neurotensin transmission itself can also impact metabolic state by exerting control over consumption, physical activity, and satiety signals. Many responses to sensory experiences and sleep processes are dictated by neurotensinergic activity via mechanisms that allow the organism to balance energy seeking and utilization to thrive in its environment. Given the broad reach neurotensin signaling has across the homeostatic landscape, understanding this system as a whole and examining new ways to target this system for therapeutic efficacy across many different conditions is necessary.
Topics: Neurotensin; Central Nervous System; Signal Transduction; Receptors, Neurotensin
PubMed: 37309600
DOI: 10.1111/jnc.15868 -
Cell Metabolism Jul 2021The lymphatic vasculature plays important roles in the physiology of the organs in which it resides, though a clear mechanistic understanding of how this crosstalk is...
The lymphatic vasculature plays important roles in the physiology of the organs in which it resides, though a clear mechanistic understanding of how this crosstalk is mediated is lacking. Here, we performed single-cell transcriptional profiling of human and mouse adipose tissue and found that lymphatic endothelial cells highly express neurotensin (NTS/Nts). Nts expression is reduced by cold and norepinephrine in an α-adrenergic-dependent manner, suggesting a role in adipose thermogenesis. Indeed, NTS treatment of brown adipose tissue explants reduced expression of thermogenic genes. Furthermore, adenoviral-mediated overexpression and knockdown or knockout of NTS in vivo reduced and enhanced cold tolerance, respectively, an effect that is mediated by NTSR2 and ERK signaling. Inhibition of NTSR2 promoted energy expenditure and improved metabolic function in obese mice. These data establish a link between adipose tissue lymphatics and adipocytes with potential therapeutic implications.
Topics: Animals; Endothelial Cells; Energy Metabolism; Lymphatic Vessels; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Neurotensin; Signal Transduction; Thermogenesis
PubMed: 34038712
DOI: 10.1016/j.cmet.2021.04.019 -
Atherosclerosis May 2024
Review
Topics: Humans; Cardiovascular Diseases; Animals; Neurotensin; Signal Transduction
PubMed: 38503610
DOI: 10.1016/j.atherosclerosis.2024.117514 -
International Journal of Molecular... Feb 2023Neurotensin (NTS) is a peptide discovered in 1973, which has been studied in many fields and mainly in oncology for its action in tumor growth and proliferation. In this... (Review)
Review
Neurotensin (NTS) is a peptide discovered in 1973, which has been studied in many fields and mainly in oncology for its action in tumor growth and proliferation. In this review of the literature, we wanted to focus on its involvement in reproductive functions. NTS participates in an autocrine manner in the mechanisms of ovulation via NTS receptor 3 (NTSR3), present in granulosa cells. Spermatozoa express only its receptors, whereas in the female reproductive system (endometrial and tube epithelia and granulosa cells), we find both NTS secretion and the expression of its receptors. It consistently enhances the acrosome reaction of spermatozoa in mammals in a paracrine manner via its interaction with NTSR1 and NTSR2. Furthermore, previous results on embryonic quality and development are discordant. NTS appears to be involved in the key stages of fertilization and could improve the results of in vitro fertilization, especially through its effect on the acrosomal reaction.
Topics: Animals; Female; Male; Mammals; Neurotensin; Humans
PubMed: 36902025
DOI: 10.3390/ijms24054594 -
Regulatory Peptides Sep 2000Neurotensin is an endogenous tridecapeptide neurotransmitter (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Try-Ile-Leu-OH) that was discovered by Carraway and Leeman in... (Review)
Review
Neurotensin is an endogenous tridecapeptide neurotransmitter (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Try-Ile-Leu-OH) that was discovered by Carraway and Leeman in bovine hypothalami in the early 1970s. Since then this peptide has been the subject of a multitude of articles detailing discoveries related to its activity, receptors, localization, synthesis, and interactions with other systems. This review article does not intend to summarize again all the history of this fascinating peptide and its receptors, since this has been done quite well by others. The reader will be directed to these other reviews, where appropriate. Instead, this review attempts to provide a summary of current knowledge about neurotensin, why it is an important peptide to study, and where the field is heading. Special emphasis is placed on the behavioral studies, particularly with reference to agonists, antagonists, and antisense studies, as well as, the interaction of neurotensin with other neurotransmitters.
Topics: Animals; Blood-Brain Barrier; Cattle; Dopamine; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Neurotensin; Oligonucleotides, Antisense; Pituitary-Adrenal System; Receptors, Neurotensin; Schizophrenia; Structure-Activity Relationship
PubMed: 11033059
DOI: 10.1016/s0167-0115(00)00183-x -
Journal of Clinical Pathology.... 1978
Topics: Blood Glucose; Central Nervous System; Digestive System; Gastric Mucosa; Humans; Hypothalamo-Hypophyseal System; Insulin; Insulin Secretion; Neurotensin; Vasodilation
PubMed: 399607
DOI: 10.1136/jcp.s1-8.1.12 -
Trends in Pharmacological Sciences Jul 1999Neurotensin is a brain and gastrointestinal peptide that fulfils many central and peripheral functions through its interaction with specific receptors. Three subtypes of... (Review)
Review
Neurotensin is a brain and gastrointestinal peptide that fulfils many central and peripheral functions through its interaction with specific receptors. Three subtypes of neurotensin receptors have been cloned. Two of them belong to the family of G protein-coupled receptors, whereas the third one is an entirely new type of neuropeptide receptor and is identical to gp95/sortilin, a 100 kDa-protein with a single transmembrane domain. In this review, the present knowledge regarding the molecular and pharmacological properties of the three cloned neurotensin receptors is summarized and the relationship between these receptors and the known pharmacological effects of neurotensin is discussed.
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Neurotensin; RNA, Messenger; Receptors, Neurotensin
PubMed: 10390649
DOI: 10.1016/s0165-6147(99)01357-7 -
Peptides Oct 2006Neurotensin (NT) can produce a profound analgesia or enhance pain responses, depending on the circumstances. Recent evidence suggests that this may be due to a... (Review)
Review
Neurotensin (NT) can produce a profound analgesia or enhance pain responses, depending on the circumstances. Recent evidence suggests that this may be due to a dose-dependent recruitment of distinct populations of pain modulatory neurons. NT knockout mice display defects in both basal nociceptive responses and stress-induced analgesia. Stress-induced antinociception is absent in these mice and instead stress induces a hyperalgesic response, suggesting that NT plays a key role in the stress-induced suppression of pain. Cold water swim stress results in increased NT mRNA expression in hypothalamic regions known to project to periaqueductal gray, a key region involved in pain modulation. Thus, stress-induced increases in NT signaling in pain modulatory regions may be responsible for the transition from pain facilitation to analgesia. This review focuses on recent advances that have provided insights into the role of NT in pain modulation.
Topics: Animals; Humans; Medulla Oblongata; Mice; Mice, Knockout; Models, Neurological; Neurotensin; Neurotransmitter Agents; Nociceptors; Pain; Periaqueductal Gray; RNA, Messenger; Receptors, Neurotensin; Spinal Cord; Stress, Physiological
PubMed: 16870306
DOI: 10.1016/j.peptides.2006.04.025 -
Current Pharmaceutical Design 2015Neurotensin (NT) is an endogenous 13 amino acid neuropeptide with profound opioid-independent analgesic effects. This role of NT is thought to be mediated by both... (Review)
Review
Neurotensin (NT) is an endogenous 13 amino acid neuropeptide with profound opioid-independent analgesic effects. This role of NT is thought to be mediated by both neurotensin receptor subtype 1 (NTS1) and neurotensin receptor subtype 2 (NTS2). NT and its receptors are widely distributed in the pain circuits in central nervous system. Thus NT might modulate pain in many structures of pain pathway, such as spinal cord, rostroventral medulla (RVM) and periaqueductal gray (PAG). Actually either intrathecal application of NT or direct injection of NT into RVM or PAG or intracerebroventricular injection of NT showed analgesic effects. NT exerted its antinociceptive effects in both acute pain and chronic pain models. The analgesic effects of NT were originally found in acute pain experiments. In the case of pathological pain, for example, formalin injection induced inflammatory pain and sciatic nerve constriction induced neuropathic pain, NT also shows antinociceptive effects. The effects exist in somatic pain as well as visceral pain induced by noxious colorectal distension (CRD) or writhing test. It should be noted that NT plays an important role in stress-induced antinociception (SIAN), especially in higher intensity stress experiments. However as a neuropeptide, NT is susceptible to degradation by peptidases and cannot cross the blood-brain barrier (BBB). Great efforts have been made to find NT analogues that are more biologically stable and could inhibit pain by systematic administration. The present review focuses on the analgesic role and the underlying mechanisms of NT and its analogues in pain, especially in chronic pain models.
Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Humans; Neurotensin; Pain
PubMed: 25345606
DOI: 10.2174/1381612820666141027124915 -
Current Opinion in Pharmacology Feb 2002Despite evidence from a variety of experimental approaches implicating the neuropeptide neurotensin in both the mechanism of action of antipsychotic drugs and the... (Review)
Review
Despite evidence from a variety of experimental approaches implicating the neuropeptide neurotensin in both the mechanism of action of antipsychotic drugs and the pathophysiology of schizophrenia, there has been some debate as to whether a peripherally administered neurotensin receptor agonist represents a sound strategy for the development of a novel class of antipsychotic drugs.
Topics: Animals; Antipsychotic Agents; Brain; Humans; Neurotensin
PubMed: 11786316
DOI: 10.1016/s1471-4892(01)00128-x