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Drug effects on neuropeptides and their receptors: Big hopes but moderate success in the treatment of chronic pain.

Neuropeptides, including tachykinins, CGRP, and somatostatin, are localized in a peptidergic subgroup of nociceptive primary afferent neurons. Tachykinins and CGRP are pronociceptive, somatostatin is an antinociceptive mediator. Intensive drug research has been performed to develop tachykinin and CGRP antagonists, and somatostatin agonists as analgesics. CGRP receptor antagonists are efficacious and well-tolerated drugs in migraine. Monoclonal antibodies against CGRP or its receptor are used for the prophylactic treatment of migraine. Tachykinin NK1 receptor antagonists failed as analgesics bu…

Effects of an herbal adaptogen feed-additive on feeding-related hypothalamic neuropeptides in chronic cyclic heat-stressed chickens.

Heat stress (HS) is a global serious issue in the poultry industry with numerous adverse effects, including increased stress, depressed feed … hypothesized that these effects may be mediated through modulation of hypothalamic feeding-related neuropeptides. Male Cobb 500 chicks were reared in 12 environmental chambers with three diets: a corn-soybean-based diet (C) and two herbal adaptogen-supplemented diets at 500 g/1000 kg (NR-PHY-500) and 1 kg/1000 kg (NR-PHY-1000). Broilers in 9 chambers were expo …

Exploring the roles of neuropeptides in trigeminal neuropathic pain: A systematic review and narrative synthesis of animal studies.

OBJECTIVE: This systematic review aims to explore the changes in expression of neuropeptides and/or their receptors following experimental trigeminal neuropathic pain in animals. DESIGN: MEDLINE, Embase, and Scopus were searched for publications up to 31st March 2021. Study selection and data extraction were completed by two independent reviewers based on the eligibility criteria. The quality of articles was judged based on the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool. RESULTS: A total of 19 studies satisfied the eligibility criteria and were …

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk.

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosteron

Direct effect of hypothalamic neuropeptides on the release of catecholamines by adrenal medulla in sheep - study ex vivo.

Stress causes the activation of both the hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal system, thus leading to the release from the adrenal medulla of catecholamines: adrenaline and, to a lesser degree, noradrenaline. It has been established that in addition to catecholamines, the adrenomedullary cells produce a variety of neuropeptides, including corticoliberine (CRH), vasopressin (AVP), oxytocin (OXY) and proopiomelanocortine (POMC) - a precursor of the adrenocorticotropic hormone (ACTH). The aim of this study was to investigate adrenal medulla activity in vitro depending, …

Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus.

Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experim…

Role of the autonomic nervous system and neuropeptides in the development of obesity in humans: targets for therapy?

Obesity and type 2 diabetes have reached epidemic proportions worldwide. These metabolic disorders, particularly obesity, are characterised by increased basal sympathetic nervous system (SNS) activity but an impaired sympathetic response to certain stimuli, such as insulin. Although targeting the SNS may seem an attractive avenue for the pharmacological prevention and treatment of obesity and related metabolic disorders, it remains unknown whether changes in SNS tone are primary and contribute to the development of these metabolic conditions or whether they develop secondary to the obese state

Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites.

The vanilloid receptor (VR1) protein functions both as a receptor for capsaicin and a transducer of noxious thermal stimuli. To determine th … tance P and calcitonin gene-related peptide, suggesting complex mechanisms for the release of these neuropeptides in response to capsaicin application.

Orexins, a novel family of hypothalamic neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner.

Orexin A and orexin B are a newly described family of orexigenic hypothalamic neuropeptides. The distribution of orexin immunoreactive fibers overlaps with the luteinizing hormone-releasing hormone (LHRH) neuronal system in the septo-preoptic area and the arcuate nucleus-median eminence region. To test the hypothesis that orexins may be involved in the regulation of pituitary LH secretion by influencing LHRH release, the effects of orexin A and orexin B on LH secretion were evaluated in ovariectomized (ovx) and ovarian steroid-treated ovx rats. Intracerebroventricular injection of orexin A or …

Immunosuppression in the definitive and intermediate hosts of the human parasite Schistosoma mansoni by release of immunoactive neuropeptides.

Evidence supporting the concept that the parasitic trematode Schistosoma mansoni may escape immune reactions from its vertebrate (man) or invertebrate (the freshwater snail Biomphalaria glabrata) hosts by using signal molecules it has in common with these hosts was obtained by the following experiments. The presence of immunoactive proopiomelanocortin (POMC)-derived peptides [corticotropin (ACTH), beta-endorphin] in, and their release from, S. mansoni was demonstrated. Coincubation of adult worms with human polymorphonuclear leukocytes or B. glabrata immunocytes led to the appearance of alpha-

Isolation, structure, and activity of -Phe-Met-Arg-Phe-NH2 neuropeptides (designated calliFMRFamides) from the blowfly Calliphora vomitoria.

Thirteen neuropeptides varying in length from 7 to 11 residues and ending C-terminally in -Phe-Met-Arg-Phe-NH2 (calliFMRFamides 1-13) and one dodecapeptide ending in -Met-Ile-Arg-Phe-NH2 (calliMIRFamide 1) have been isolated from thoracic ganglia of the blowfly Calliphora vomitoria. Different repeating patterns of amino acid sequences enable the peptides to be arranged into distinct groups. One such group of five nonapeptides has the sequence Xaa-Pro-Xaa-Gln-Asp-Phe-Met-Arg-Phe-NH2. Three peptides in this group, with the N-terminal tripeptide sequences Thr-Pro-Gln-, Thr-Pro-Ser-, and Ser-Pro-S…

Identification of neuropeptides in pelvic and pudendal nerve afferent pathways to the sacral spinal cord of the cat.

The distribution of several neuropeptides, including vasoactive intestinal polypeptide (VIP), substance P, somatostatin, leucine enkephalin, methionine enkephalin, and cholecystokinin, in sacral afferent pathways of the cat was examined by immunohistochemical techniques. Certain peptides (substance P, somatostatin, and leucine enkephalin) could be demonstrated in normal dorsal root ganglion cells; however, topical administration or injections of colchicine solution into ganglia 36-56 hours prior to removal markedly increased the number of cells labeled and the intensity of staining. Other pept…

Comparison of the solution structures of the chimeric peptides galanin(1-12)-Ala-neuropeptide Y(25-36)amide and galanin(1-12)-Pro-neuropeptide Y(25-36)amide.

In a previous study [Arvidsson, K., Land, T., Langel, U., Bartfai, T. & Ehrenberg, A. (1993) Biochemistry 32, 7787-7798], the 25-amino-acid-residue chimeric peptide M32, galanin(1-12)-Pro-neuropeptide Y(25-36)amide, was found to bind very strongly to galanin receptors and also to have considerable affinity to neuropeptide Y receptors. The solution structure of M32 in 30% (by vol.) 1,1,1,3,3,3-hexafluoro-2-propanol, was determined from structural restraints obtained by two-dimensional 1H-NMR. Another peptide, M88, with Ala instead of Pro in position 13, was shown to bind with tenfold lower affi

A Tale of Two States: Similarities and Differences in Neuropeptide Signaling in Larval and Adult Drosophila.

Having the life cycle divided into a larval and an adult stage, each dwelling in a separate habitat, is advantageous since it prevents competition for resources and separates development and reproduction into different stages. In holometabolous insects, larval life is characterized by intense feeding, growth, and molting, whereas the adults constitute the reproductive and highly mobile stage. This review discusses how this switch in lifestyle is reflected in the neuroendocrine system and peptidergic signaling. Neuropeptides and peptide hormones (collectively NPHs) are important regulators of m…

Photocaged Oxytocin and Vasopressin Probes to Decipher Neuropeptide Signalling With High Spatiotemporal Resolution.

The oxytocin/vasopressin (OT/VP) neuropeptide signalling system is essential for regulating social behaviour, emotion, learning, and memory, and its dysregulation is associated with multiple neurological disorders. However, accurately studying OT/VP signalling in the brain remains difficult due to widespread receptor expression, long peptide half-lives, and extensive diffusion. To address these challenges, we investigated three classes of photolabile protecting groups-coumarin, nitrophenylpropyl, and borondipyrromethene-to enable precise, light-triggered OT/VP release. These photocages allow c

Paternal lactational overnutrition induces sex-dependent hypothalamic neuropeptide programming in offspring.

Childhood obesity can induce long-lasting metabolic programming, with consequences that may extend to subsequent generations. However, wheth … trol females to generate F1 offspring. In adulthood, hypothalamic mRNA expression of the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related peptide (AgRP) and the anorexigenic neuropeptides proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), as well as plasma leptin concentrations and food intake, were evaluated. M …

Pancreatic polypeptide interacts with neuropeptide Y4 receptor to promote hepatocellular carcinoma progression.

Pancreatic polypeptide (PP) and neuropeptide Y4 receptor (Y4R) are part of a conserved system that is involved in appetite regulation, gastrointestinal functions, and energy homeostasis. Experimental evidence suggests that PP-Y4R signaling might play a role in various extrahepatic cancer types, but the exact mechanisms remain unclear. Moreover, the potential role of PP-Y4R crosstalk in hepatocellular carcinoma (HCC) was unknown and has been addressed in this study. We found that the ligand (PP) and the receptor (Y4R) were markedly overexpressed in HCC cells and in patient-derived tissues, whic

Neuropeptide TIP39 as a pluripotent brain molecule and its potential functions in postpartum depression.

BACKGROUND: The tuberoinfundibular peptide of 39 residues (TIP39) is a small peptide first extracted in 1997, which has garnered limited research attention. It belongs to the parathyroid hormone (PTH)-related peptides family and specifically binds the parathyroid receptor type 2 (PTH2R). It is gaining attention for its roles in mood regulation, maternal behavior, and social functions. Its potential in modulating these processes possibly positions TIP39 as an underexplored candidate for exploring complex physiological functions of postpartum depression. AIMS: Given the accumulating evidence of

Modulation of aggression by neuropeptide Y: receptor pharmacology, neural circuitry, and psychiatric relevance.

Violence and aggression arise from dynamic interactions among genetic liability, neurobiological regulation, and environmental stressors, mediated by a distributed "core aggression circuit" encompassing the prefrontal cortex, amygdala, hypothalamus, and brainstem. Neuropeptide Y (NPY), a highly conserved 36-amino acid neuromodulator, has emerged as a key stress-buffering and emotion-regulatory agent with relevance to impulsive and reactive aggression. This review synthesizes translational evidence linking NPY biology to aggression and violence by integrating molecular mechanisms, receptor phar

Роль Neuroptide Y в зубной касти: уравновешивание нейрогенного воспаления и модуляции боли.

ВЕЩЕСТВО: Стоматологическая целлюлоза представляет собой густонаселенную, низкосопоставимую ткань, в которой нейронное воспаление может быстро перерасти в отеку, поднимает внутрипульсовое давление, микроваскулярный компромисс и боль. В то время как пептид вещества P (SP) и кальцитонин (CGRP) являются хорошо зарекомендовавшими себя движущими силами вазодиляции целлюлозы, внутренний контррегулятивный механизм Neuroopepide Y (NPY) остается относительно недостаточно изученным.ЦЕЛИ: Критически синтезировать текущие данные по NPY в области стоматологической биологии целлюлозы с уделением особого вни

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… This evidence suggests a model in which NPY may counterbalance the effects of sensory neuropeptides in the dental pulp, as dry eye disease is also governed by neuropeptides (Hwang et al. 2021 ). … Search Strategy MEDLINE/PubMed (“Neuropeptide Y”[Mesh] OR “Neuropeptide Y” OR NPY OR “neuropeptides”) AND (“Dental Pulp”[Mesh] OR “dental pulp” OR pulp OR “pulp tissue”) AND (Inflammation OR “neurogenic inflammation” OR “pulpal inflammation” OR “dentinal hypersensitivity” OR “dentine hypersensitivity …