neuropeptide-y and Neoplasms

As a very abundant neuropeptide in the brain and widely distributed peptide hormone in the periphery, neuropeptide Y (NPY) appears to be a multisignaling key peptide. Together with peptide YY, pancreatic polypeptide and the four human G protein-coupled receptor subtypes hY1R, hY2R, hY4R and hY5R it forms the NPY/hYR multiligand/multireceptor system, which is involved in essential physiological processes as well as in human diseases. In particular, NPY-induced hY1R signaling plays a central role in the regulation of food intake and stress response as well as in obesity, mood disorders and cancer. Thus, several hY1R-preferring NPY analogs have been developed as versatile tools to unravel the complex NPY/hY1R signaling in health and disease. Further, these peptides provide basic lead structures for the development of innovative drugs. Here, the current research is summarized focusing on the development of differently sized hY1R-preferring NPY analogs as well as their advances with respect to hY1R profiling, potential therapeutic applications and targeted cancer imaging and therapy. Finally, major limitations and innovative strategies for next generation hY1R-preferring NPY analogs are addressed.

Topics: Humans; Neoplasms; Neuropeptide Y; Receptors, Neuropeptide Y

Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

Topics: Adipokines; Agouti-Related Protein; Animals; Brain-Derived Neurotrophic Factor; Extracellular Signal-Regulated MAP Kinases; Female; Gonadal Steroid Hormones; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Male; Membrane Proteins; Mice; MicroRNAs; Neoplasms; Neuropeptide Y; Obesity; Pro-Opiomelanocortin; Receptor, Melanocortin, Type 4; Receptors, Leptin

NPY, PYY and PP constitute the so-called NPY hormone family, which exert its biological functions in humans through YRs (Y₁, Y₂, Y₄ and Y₅). Systematic modulation of YR function became important as this multireceptor/multiligand system is known to mediate various essential physiological key functions and is involved in a variety of major human diseases such as epilepsy, obesity and cancer. As several YRs have been found to be overexpressed on different types of malignant tumors they emerge as promising target in modern drug development. Here, we summarize the current understanding of YRs function and the molecular mechanisms of ligand binding and trafficking. We further address recent advances in YR-based drug design, the development of promising future drug candidates and novel approaches in YR-targeted tumor diagnostics and therapy opportunities.

Topics: Drug Design; Humans; Ligands; Molecular Structure; Neoplasms; Neuropeptide Y; Obesity; Pancreatic Polypeptide; Peptide YY; Protein Isoforms; Receptors, Neuropeptide Y

The neuropeptide Y (NPY) system--comprising of neuropeptide Y, peptide YY, pancreatic polypeptide and the corresponding Y receptors through which they act (Y1, Y2, Y4, Y5 and y6)--is well known for its role in the regulation of energy homeostasis and associated processes. Dysfunctions of the system have been implicated in human diseases such as obesity and cancer, raising the possibility that correction of the system may provide therapeutic benefits for these diseases. In addition to the regulation of appetite and satiety that has attracted most attention during the past years, insight has also been gained into the critical role of NPY in the control of energy expenditure, oxidative fuel selection and bone metabolism. Studies using conditional knockout models further shed light on the central versus peripheral, and hypothalamic versus extra-hypothalamic mechanisms of these regulatory effects of NPY. Moreover, a role of NPY family peptides and Y receptors in modulating the growth of tumours has emerged. These findings provide the basis for novel NPY system-targeted strategies to treat obesity as well as cancer. Such strategies include modifying both sides of the energy balance equation--energy intake versus energy expenditure--to achieve a greater weight/fat loss by particularly modulating peripheral Y receptor(s) to ameliorate metabolic conditions without interfering with central functions of Y receptors. In addition, targeting multiple Y receptors and/or multiple systems involved in the regulation of energy balance will have greater beneficial effects. However, long-term interference with the NPY system to target obesity or cancer related aspects needs to consider potential side effects on bone health.

Topics: Animals; Energy Intake; Energy Metabolism; Humans; Molecular Targeted Therapy; Neoplasms; Neuropeptide Y; Obesity

Cancer anorexia frequently characterizes the clinical journey of patients with cancer and affects patients' morbidity, mortality, and quality of life. A constellation of symptoms concur to the diagnosis of anorexia, and early satiety, changes in taste/smell, and nausea are the more frequently reported. The pathogenesis of cancer anorexia is multifactorial, but accumulating evidence indicates that the hypothalamic melanocortin and neuropeptide Y systems become resistant to peripheral inputs. This results in increased melanocortin activity and reduced neuropeptide Y function, thereby leading to the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Interestingly, hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. In the clinical setting, cancer anorexia develops with heterogeneous presenting symptoms (i.e., early satiety and/or nausea and/or changes of taste) and varying degrees of severity. Available evidence suggests that the constellation of symptoms characterizing this syndrome should be considered, at least in part, as different phenotypes of common neurochemical/metabolic alterations in the presence of a chronic inflammatory state.

Topics: Anorexia; Biogenic Monoamines; Brain; Humans; Hypothalamus; Melanocortins; Neoplasms; Neuropeptide Y

Nitric oxide (NO), a molecule with multidimensional effects has generated exponential amount of research since its identification as a biological messenger almost two decades back. The recent trend in NO research is to explore newer dimensions in the cellular and molecular mechanisms of actions and interactions of NO with various biomolecules and their implications in various pathophysiological states. Advances in our knowledge of the mechanisms by which this pleiotropic molecule regulates the expression of eukaryotic genes has generated considerable excitement and is paving the way for development of novel NO based therapeutic strategies. However, it is still a challenge to understand fully the paradox of beneficial and damaging effects of this exciting molecule. This review will discuss the current trends of research in this area especially highlighting the new insights gained from recent experimental and clinical studies. New approaches to reduce or augment the availability of NO to benefit a wide range of clinical conditions and avenues for future research are also briefly discussed.

Topics: Animals; Biomedical Research; Cell Adhesion Molecules; Cytokines; Estrogens; Gene Expression; Heat-Shock Proteins; Humans; Melatonin; Mitochondria; Natriuretic Peptides; Neoplasms; Neuroimmunomodulation; Neuronal Plasticity; Neuropeptide Y; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Opioid Peptides; Oxytocin; Seizures; Steroids; Stress, Physiological

The peptides pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY) share a similar structure, known as PP-fold. Within this family of peptides, NPY, a highly conserved 36-aminoacid residue peptide, is involved in the regulation of a wide range of physiological functions, such as food intake and energy metabolism, as well as in the promotion of some remarkable aspects of tumor progression, including cell proliferation, matrix invasion, metastatization, and angiogenesis. NPY exerts its biological effects through five G-protein coupled receptors, named Y1-, Y2-, Y4-, Y5-, and y6-R, which appear associated with different aspects of oncogenesis. Y1-R seems involved in the modulation of cancer cell proliferation, whereas Y2-R activation appears to promote angiogenesis. The development of NPY receptor subtype selective analogs has helped to elucidate the physiological and pathophysiological role and localization of each receptor and may contribute to a better understanding of the receptor-ligand interaction. The NPY system appears to be variously associated with specific tumors, including neural crest-derived tumors, breast and prostate cancers. In addition to NPY, PYY is also able to affect cancer cell growth in a dose-dependent manner and through Y-Rs. In conclusion, peptides of the NPY family and the related receptors play an important role in the progression of different cancer types, with some molecular specificity according to each step of this process. On this basis, future studies may be directed to the implementation of novel diagnostic and therapeutic approaches targeting this system.

Topics: Animals; Cell Growth Processes; Disease Progression; Humans; Neoplasms; Neovascularization, Pathologic; Neuropeptide Y

Cachexia is among the most debilitating and life-threatening aspects of cancer. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome continues to lead to effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide, all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the underlying malignancy. As weight loss shortens the survival time of cancer patients and decreases their performance status, effective therapy would extend patient survival and improve quality of life.

Topics: Adipose Tissue; Agouti Signaling Protein; Anorexia; Anti-Anxiety Agents; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Appetite Stimulants; Cachexia; Cytokines; Energy Metabolism; Gastrointestinal Agents; Glucocorticoids; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Neoplasms; Neuropeptide Y; Patient Care Team; Progesterone; Signal Transduction; Starvation; Syndrome

Tumor markers are developmentally regulated proteins or carbohydrate molecules, which are expressed in specific tissues in the fetus during certain developmental periods. With malignant transformation, these molecules are reexpressed in neoplastic tissues. Some developmental or metabolic disorders can also lead to the expression of tumor marker genes, hereditary tyrosinaemia and ataxia teleangiectasia associating with elevated serum alpha-fetoprotein are examples of such conditions. In pediatric malignancies, the most common markers in clinical use are alpha-fetoprotein in liver and yolk sac tumors, chorionic gonadotropin in germ cell tumors, and catecholamines and neuron specific enolase in neuroblastoma. Several other molecules including carbohydrate antigens CA 19-9 and CA 125 may also have a role in the diagnosis and follow-up of distinct types of childhood malignancies. The non-specificity of several markers, such as tissue polypeptide antigen and sialic acid, greatly hampers their clinical use. In this review we will discuss the biology and current knowledge on the use of serum and urine tumor markers. We also highlight the putative future use of these molecules in cancer diagnosis and therapy, including the use of monoclonal antibodies directed against these antigens.

Topics: alpha-Fetoproteins; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Catecholamines; Child; Chorionic Gonadotropin; Chromogranin A; Chromogranins; Humans; Infant, Newborn; N-Acetylneuraminic Acid; Neoplasms; Neuropeptide Y; Peptides; Phosphopyruvate Hydratase; Radioimmunodetection

The safety of radiotherapy techniques in the treatment of vestibular schwannoma (VS) shows a high rate of tumor control with few side effects. Neuropeptide Y (NPY) may have a potential relevance to the recurrence of VS. Further research is still needed on the key genes that determine the sensitivity of VS to radiation therapy.. Transcriptional microarray data and clinical information data from VS patients were downloaded from GSE141801, and vascular-related genes associated with recurrence after radiation therapy for VS were obtained by combining information from MSigDB. Logistics regression was applied to construct a column line graph prediction model for recurrence status after radiation therapy. Pan-cancer analysis was also performed to investigate the cooccurrence of these genes in tumorigenesis.. We identified eight VS recurrence-related genes from the GSE141801 dataset. All of these genes were highly expressed in the VS recurrence samples. Four collagen family genes (. Four collagen family genes have been identified as possible predictors of recurrence after radiation therapy for VS. Pan-cancer analysis reveals potential associations between the pathogenesis of VS and other tumorigenic factors. The relevance of NPY to VS was also revealed for the first time.

Topics: Collagen; Collagen Type III; Collagen Type IV; Collagen Type V; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Logistic Models; Neoplasm Recurrence, Local; Neoplasms; Neovascularization, Pathologic; Neuroma, Acoustic; Neuropeptide Y; Tumor Microenvironment

G-protein-coupled receptors like the human Y

Topics: Boranes; Boron; Boron Neutron Capture Therapy; Drug Carriers; Drug Delivery Systems; HEK293 Cells; Humans; MCF-7 Cells; Neoplasms; Neuropeptide Y; Receptors, Neuropeptide Y

Knowledge of genes essential for the life-extending effect of dietary restriction (DR) in mammals is incomplete. In this study, we found that neuropeptide Y (Npy), which mediates physiological adaptations to energy deficits, is an essential link between DR and longevity in mice. The lifespan-prolonging effect of lifelong 30% DR was attenuated in Npy-null mice, as was the effect on the occurrence of spontaneous tumors and oxidative stress responses in comparison to wild-type mice. In contrast, the physiological processes activated during adaptation to DR, including inhibition of anabolic signaling molecules (insulin and insulin-like growth factor-1), modulation of adipokine and corticosterone levels, and preferential fatty acid oxidation, were unaffected by the absence of Npy. These results suggest a key role for Npy in mediating the effects of DR. We also provide evidence that most of the physiological adaptations to DR could be achieved in mice without Npy.

Topics: Animals; Caloric Restriction; Fatty Acids; Female; Insulin; Insulin-Like Growth Factor I; Longevity; Male; Mice; Neoplasms; Neuropeptide Y; Oxidation-Reduction; Oxidative Stress

Pro-protein convertase-2 (PC2) and carboxypeptidase-E (CPE) proteins are two major members of the pro-protein convertases that involve in the maturation of protein precursor. By using PC2 activity, immunocytochemistry (ICC) and Western blot method, PC2, CPE and preproNPY protein expression levels were compared among mature retina tissue, RGC-5 cells and its differentiated cells, or brain cortex tissue, NS20Y tumor cells and its differentiated cells, or mature breast tissue, breast tumor cell RM1 and breast adenocarcinoma tissue. The experimental results indicated that the differentiated cells or tissues had higher or highest PC2 activity. In the comparative experiments, more PC2 protein expression in the mature tissues and more CPE and preproNPY protein expression in the tumor cells or tumor tissue were observed, but no expression of preproNPY protein was observed in the mature tissues. Compared with NS20Y or RGC-5 undifferentiated cells, its differentiated cells showed less proPC2, more proCPE and more preproNPY protein expressions. The results demonstrated that the mature tissues showed stronger PC2/CPE-mediated pro-protein processing ability than the tumor cells or tissue. The results also showed that the artificial differentiation of RGC-5 or NS20Y cells was different from maturation of its corresponding normal tissue.

Topics: Adenocarcinoma; Animals; Breast Neoplasms; Carboxypeptidase H; Cell Differentiation; Cell Line, Tumor; Cerebral Cortex; Mice; Neoplasms; Neuropeptide Y; Proprotein Convertase 2; Protein Precursors; Protein Processing, Post-Translational; Rats; Retina

The successful use of peptides as potential radiopharmaceuticals essentially requires the modification of the bioactive peptide hormones to introduce chelators for radiolabeling. In this study, four Y 1/Y 2 receptor-selective NPY analogues with different receptor subtype specificities have been investigated. For in vitro studies, the cold metal surrogate was used. Gallium and indium complexes were introduced by using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid as bifunctional chelator. The peptides were synthesized by solid-phase peptide synthesis (SPPS), the chelator was coupled either at the N-terminus or at the N(epsilon) side chain of Lys(4) of the resin-bound peptide, and the labeling was performed in solution after cleavage. Competitive binding assays showed high binding affinity of the receptor-selective analogues at NPY receptor expressing cells. To test internalization of the novel peptide analogues and the metabolic stability in human blood plasma, the corresponding 5(6)-carboxyfluorescein (CF) analogues were prepared and investigated. One of the most promising analogues, the Y 1-receptor selective [Lys(DOTA)(4), Phe(7), Pro(34)]NPY was labeled with (111)In and injected into nude mice that bear MCF-7 breast cancer xenografts, and biodistribution studies were performed. In vitro and in vivo studies suggest that receptor-selective analogues of NPY have promising characteristics for future applications in nuclear medicine for breast tumor diagnosis and therapy.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Cattle; Cell Line; Cell Line, Tumor; Chelating Agents; Heterocyclic Compounds, 1-Ring; Humans; Indium Radioisotopes; Ligands; Mice; Neoplasms; Neuropeptide Y; Receptors, Neuropeptide Y; Staining and Labeling; Tissue Distribution

Tumor growth leads to cancer anorexia that is ameliorated using omega-3 fatty acids (omega-3FA). We hypothesize that omega-3FA modulates up-regulation of hypothalamic orexigenic neuropeptide Y (NPY) and down-regulation of anorexigenic alpha melanocyte-stimulating hormone (alpha-MSH) and serotonin 1B receptors (5-HT(1B)-receptors) in tumor-bearing rats.. Twenty-eight tumor-bearing rats were fed either chow (TB-Control) or omega-3FA (TB-omega-3FA). When anorexia developed in TB-Control rats, they and a cohort of TB-omega-pi-3 rats were killed. The rest had their tumor resected (R-Control and R-omega-3FA), and when anorexic TB-Controls normalized their food intake, brains were removed for hypothalamic immunocytochemical study of NPY, alpha-MSH, and 5-HT(1B)-receptor antibodies concentrations. Comparison among slides were assessed by image analysis and analyzed by ANOVA and t test.. At anorexia, hypothalamic NPY in arcuate nucleus (ARC) increased by 38% in TB-omega3FA versus TB-Control, whereas alpha-MSH decreased 64% in ARC and 29% in paraventricular nucleus (PVN). Omega-3FA diet in anorexia (TB-omega-3FA vs R-omega-3FA) produced similar qualitative changes of NPY (22% increase) and alpha-MSH (31% decrease) in ARC, with concomitant decrease of 37% in 5-HT(1B)-receptors in PVN, confirming the influence of omega-3FA on the hypothalamic food intake modulators. However, after tumor resection (TB-Control vs R-Control) a 97% increase in NPY and a 62% decrease in alpha-MSH occurred that was significantly greater than in rats fed omega-3FA diet.. Tumor resection and omega-3FA modifies hypothalamic food intake activity, up-regulating NPY and down-regulating alpha-MSH and 5-HT(1B)-receptors. Tumor resection in anorexic rats on chow diet restored hypothalamic NPY, alpha-MSH, and food intake quantitatively more than in rats fed omega3FA diet.

Topics: Animal Feed; Animals; Anorexia; Appetite; Down-Regulation; Eating; Fatty Acids, Omega-3; Hypothalamus; Male; Neoplasms; Neuropeptide Y; Rats; Rats, Inbred F344; Receptor, Serotonin, 5-HT1B; Up-Regulation

This study investigated leptin and neuropeptide Y levels in children with cancer, the relationship of those levels to cachexia, and their usefulness as prognostic indicators. Twenty-three newly diagnosed children with cancer were included in the study. The median age at diagnosis was 8 years (range 1.5-14), and the male to female ratio was 13:10. Body mass index, serum leptin and neuropeptide Y levels were measured at diagnosis and at each cycle of chemotherapy. The mean neuropeptide Y level was 211.1 pmol/l at diagnosis and decreased to 92.8 pmol/l at the fifth cycle of chemotherapy. In contrast, the mean leptin level was 3.9 ng/ml at diagnosis and increased to 13.0 ng/ml at the fifth cycle of chemotherapy. Thus, levels of these factors are influenced by treatment status and disease progression. The mean neuropeptide Y level at diagnosis was 82.32 pmol/l in children with complete remission and 430.16 pmol/l in those who died with disease during the follow-up period. The mean leptin level at diagnosis was 6.60 ng/ml in children with complete remission and 0.192 ng/ml in patients who died with disease during the follow-up period. The neuropeptide Y and leptin levels seem to be related to prognosis and could be used as prognostic indicators in the follow-up of children with cancer.

Topics: Adolescent; Anorexia; Biomarkers; Cachexia; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Leptin; Male; Neoplasms; Neuropeptide Y; Prognosis; Weight Loss

Anorexia is a noxious symptom, and over half of patients with advanced cancer experience it. Neuropeptide Y (NPY), leptin, and cholecystokinin 8 (CCK8) have been implicated.. This exploratory study 1) compared circulating concentrations of NPY and leptin between anorectic cancer patients and historic controls and 2) explored whether NPY, leptin, or CCK8 may serve as correlates of anorexia severity. Cancer patients met predefined eligibility criteria: 1) weight loss > or = 2.3 kg over the preceding 2 months and/or a physician-estimated caloric intake of < 20 calories per kilogram of body weight per day and 2) patient acknowledgment that appetite or weight loss was an ongoing problem.. Seventy-three cancer patients were studied, and > 90% reported a > or = 50% decline in appetite from baseline in the preceding 2 months. NPY levels were lower than control values: mean +/- standard deviation, 466 pg/mL +/- 161 pg/mL versus 560 pg/mL +/- 151 pg/mL, respectively (P = 0.004). Because a few (but not all) earlier studies suggested an age-related decline in NPY levels, a subgroup analysis was performed and found no age-adjusted difference in NPY levels between groups. Similarly, leptin concentrations were not different between groups. Significant correlations were not observed between anorexia severity and NPY, leptin, or CCK8 levels.. There were no differences in leptin and CCK8 levels between anorectic cancer patients and historic controls. Circulating concentrations of NPY, leptin, and CCK8 did not correlate with anorexia severity. However, the current results suggest a need for further examination of NPY in cancer-associated anorexia.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Cholecystokinin; Female; Humans; Leptin; Male; Middle Aged; Neoplasms; Neuropeptide Y; Peptide Fragments

We previously reported that the human melanoma cell line, SEKI, induces severe weight loss in nude mice. In the present study, we examined the expression of weight-regulating neuropeptide mRNAs in the hypothalamus of this cancer cachectic model by using a sensitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method and in situ hybridization. mRNA levels of neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) in the whole hypothalamus were elevated significantly in the SEKI mice as compared with control mice. In situ hybridization showed that NPY and CRH mRNA were upregulated in the arcuate nucleus and the paraventricular nucleus, respectively. There were no significant differences in melanin-concentrating hormone (MCH), orexin (OX), and cholecystokinin mRNA levels between the SEKI and control mice. These results suggest that the NPYergic system is functioning in the rodent model of cancer cachexia; however, the role of the CRHergic system in energy homeostasis remains to be elucidated. This is the first report of the hypothalamic neuropeptide response to cachexia-inducing human cells.

Topics: Animals; Appetite Regulation; Arcuate Nucleus of Hypothalamus; Body Weight; Cachexia; Corticotropin-Releasing Hormone; DNA Primers; Female; Histocytochemistry; Humans; Hypothalamus; In Situ Hybridization; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Neuropeptide Y; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

A parallel increase in systemic plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) was found during thoracotomy and surgery involving cardiopulmonary bypass in man. Thus, plasma levels of NPY-LI increased from 29 +/- 4 pmol/l before anaesthesia to 59 +/- 10 after thoracotomy and to 87 +/- 8 pmol/l upon cardiopulmonary bypass. The corresponding NA levels increased from 1.3 +/- 0.1 nmol/l before anaesthesia to 3.0 +/- 0.6 and 4.2 +/- 5 nmol/l after thoracotomy and cardiopulmonary bypass, respectively. A significant correlation was found between plasma levels of NPY-LI and NA during the operation but not between NPY-LI and adrenaline. The NPY-LI in human plasma was found to be similar to synthetic porcine NPY on reversed phase high performance liquid chromatography. Human submandibular arteries contained high levels of NPY-LI (24 +/- 3 pmol/g). In in vitro experiments on isolated human submandibular arteries, NPY in low concentrations (1000 pmol/l) was found to potentiate the contractile effects of NA or transmural nerve stimulation and to exert vasoconstrictor activity per se in higher concentrations. The calcium-entry antagonist nifedipine abolished both the NPY-induced contractions and the enhancement of NA-evoked contractions. NPY depressed the nerve stimulation-evoked 3H-NA release from human submandibular arteries via a prejunctional mechanism which was resistant to nifedipine. NPY contracted human mesenteric veins and renal arteries, but not mesenteric arteries. In conclusion, NPY seems to be co-released with NA upon sympathetic activation in man. Furthermore, NPY exerts both pre- and postjunctional effects on sympathetic control of human blood vessels.

Topics: Adult; Animals; Arteries; Blood Pressure; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Chromatography, High Pressure Liquid; Electric Stimulation; Female; Heart Rate; Humans; Male; Middle Aged; Neoplasms; Nerve Tissue Proteins; Neuropeptide Y; Nifedipine; Norepinephrine; Peripheral Nerves; Swine; Thoracic Surgery; Vascular Resistance