Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothalamic satiety peptide CART (cocaine and amphetamine regulated transcript) is expressed at high levels in anorectic rat glucagonomas but not in hypoglycemic insulinomas. However, a non-anorectic metastasis derived from the glucagonoma retained high CART expression levels and produced circulating CART levels comparable to that of the anorectic tumors. Moreover, distinct glucagonoma lines derived by stable HES-1 transfection of the insulinoma caused severe anorexia but retained low circulating levels of CART comparable to that of insulinoma bearing or control rats. Islet tumor associated anorexia and circulating CART levels are thus not correlated, and in line with this peripheral administration of CART (5-50 mg/kg) produced no effect on feeding behavior. In the rat two alternatively spliced forms of CART mRNA exist and quantitative PCR revealed expression of both forms in the hypothalamus, in the different islet tumors, and in the islets of Langerhans. Immunocytochemistry as well as in situ hybridization localized CART expression to the somatostatin producing islet D cell. A potential endocrine/paracrine role of islet CART remains to be clarified.
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PMID:The hypothalamic satiety peptide CART is expressed in anorectic and non-anorectic pancreatic islet tumors and in the normal islet of Langerhans. 1021 34

The neuropeptides orexin-A and orexin-B are produced in neurons of the lateral hypothalamic area and have been implicated to be involved in the regulation of food/water intake and sleep-wake control. The orexins act at two different G-protein-coupled orexin receptors (OX-R1 and OX-R2) that are derived from separate genes and expressed differentially throughout the central nervous system. In the present study, we have used a polyclonal antipeptide antiserum to analyse in detail the distribution of OX-R1-immunoreactive neurons in the rat hypothalamus. In order to identify the chemical mediators of orexin action in the hypothalamus, the OX-R1-containing neurons were characterized with regard to the content of peptides shown previously to affect ingestive and drinking behaviour. Neurons containing OX-R1 immunoreactivity were widely distributed in the hypothalamus with cell bodies located in the suprachiasmatic, periventricular, paraventricular (both magno- and parvocellular division), supraoptic, arcuate, ventromedial, dorsomedial and tuberomammillary nuclei and the lateral hypothalamic area. In magnocellular neurons of the paraventricular and supraoptic nuclei, OX-R1 immunoreactivity was seen in both vasopressin- and oxytocin-containing neurons. OX-R1 immunoreactivity was demonstrated in vasopressin and vasoactive intestinal polypeptide (VIP) neurons of the suprachiasmatic nucleus, in somatostatin neurons of the periventricular nucleus and in corticotropin-releasing hormone (CRH) neurons of the parvocellular paraventricular nucleus. In the arcuate nucleus, OX-R1 immunoreactivity was present in neuropeptide Y (NPY) and agouti-related peptide (AGRP) neurons of the ventromedial part as well as in proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) neurons of the ventrolateral division. In the lateral hypothalamic area, OX-R1 immunoreactivity was demonstrated in melanin-concentrating hormone (MCH)- and orexin-containing neurons. In the hypothalamic tuberomammillary nucleus, OX-R1-immunoreactivity was shown in many histamine-containing neurons. The results support the idea that orexins have important actions on hypothalamic neurons that control food intake and fluid balance, but also that orexins may regulate other neuroendocrine systems.
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PMID:Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake. 1184 98

A cDNA membrane array displaying 1183 probes was used to detect hypothalamic and pituitary changes in gene expression accompanying ageing and age-associated pituitary macroadenomas. Four groups of male Sprague-Dawley rats (3-, 15-, 24-month-old and 24-month-old with prolactinoma) were compared in two independent hybridizations. cDNA array data were confirmed and completed by comparative reverse transcriptase-polymerase chain reaction on selected genes. The expression of 454 and 116 mRNAs was detected in hypothalamus and pituitary, respectively. Growth hormone (GH) mRNA alone represented 85% of total gene expression in the gland of young rats, and other pituitary hormone transcripts 2.8%, while melanin-concentrating hormone (MCH) mRNA, the most expressed neuropeptide transcript involved in neuroendocrine regulation, accounted for only 0.8% of total hypothalamic transcripts. The proportion of genes modified in the hypothalamus and pituitary was rather modest: 1.5% and 5.2%, respectively, for ageing per se, and 1.1% and 5.2% for age-associated macroprolactinomas. Among pituitary specific RNAs, GH mRNA expression was notably decreased with age. At the hypothalamic level, expression of genes directly involved in GH regulation, such as somatostatin and growth hormone-releasing hormone, was not altered, while neuropeptide transcripts involved in feeding behaviour [orexin/hypocretin, MCH, pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART)] were significantly altered. In addition, a few ubiquitous transcripts (hnRNP-K, PFKm, CCND 2, calponin and set) were differently affected in both tissues. Modifications in hypothalamic orexigenic (orexin, MCH) and anorexigenic (POMC, CART) gene expression are in keeping with an age-associated decrease in energy consumption but a higher one in the presence of macroprolactinomas.
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PMID:Age-associated changes in hypothalamic and pituitary neuroendocrine gene expression in the rat. 1271 10

Cocaine- and amphetamine-regulated transcript-immunoreactive (CART-IR) neurons and nerve fibers were abundant in the submucosal and myenteric plexuses of the guinea pig duodenum, ileum, cecum, proximal and distal colon. CART immunoreactivity was also observed in cell bodies and nerve fibers in the extrahepatic biliary tract. In the myenteric plexus, similar proportions (~20-25%) of neurons were CART-IR in all regions, with the exception of the cecum, where only 13% were CART-IR. In the submucosal plexus, CART-IR was detected in 35-50% of the neurons along the bowel with the exception of the proximal colon (~10%). Multiple label immunohistochemistry in the myenteric plexus of the ileum demonstrated that CART-IR neurons were also immunoreactive for choline acetyltransferase (83%), tachykinins (77%), calbindin (50%), nitric oxide synthase (20%), and/or vasoactive intestinal peptide (23%). In triple label studies, we found that ~8% of the CART-IR neurons were also immunoreactive for both choline acetyltransferase and nitric oxide synthase. CART immunoreactivity was not colocalized with calretinin, somatostatin, or serotonin. These results, combined with previous studies of chemical coding and projection patterns in the guinea pig ileum, indicate that at least four different classes of gut neurons in the myenteric plexus express CART peptide, including excitatory and inhibitory motor neurons projecting to the circular muscle, intrinsic primary afferent neurons, and a subset of descending interneurons. Because all CART-IR neurons in the submucosal plexus were also vasoactive intestinal peptide-IR, they are likely to include secretomotor/vasodilator neurons.
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PMID:Distribution and chemical coding of cocaine- and amphetamine-regulated transcript peptide (CART)-immunoreactive neurons in the guinea pig bowel. 1276 8

CART peptides have emerged as important islet regulators. CART is expressed both in islet endocrine cells and in parasympathetic and sensory nerves innervating the islets. In adult rats the intra-islet expression of CART is limited to the somatostatin producing delta-cells, while in adult mice CART is mainly expressed in nerve fibers. During development islet CART is upregulated; in rats in almost all types of islet endocrine cells, including the insulin-producing beta-cells, and in mice mainly in the alpha-cells. This pattern of expression peaks around birth. CART is also expressed in human pancreatic nerves and in islet tumours where the expression level of CART may be related to the degree of differentiation of the tumour. Interestingly, in several rat models of type 2 diabetes CART expression is robustly upregulated in the beta-cells, and is prominent during the phase of beta cell proliferation and hypertrophy. While CART inhibits glucose stimulated insulin secretion from rat islets it augments insulin secretion amplified by cAMP. Mice lacking CART, on the other hand, have islet dysfunction, and humans with a missense mutation in the cart gene are prone to develop type 2 diabetes. These data favor a role of CART in normal islet function and in the pathophysiology of type 2 diabetes.
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PMID:CART is a novel islet regulatory peptide. 1684 87

In adults, the adipocyte-derived hormone, leptin, regulates food intake and body weight principally via the hypothalamic arcuate nucleus (ARC). During early postnatal development, leptin functions to promote the outgrowth of neuronal projections from the ARC, whereas a selective insensitivity to the effects of leptin on food intake appears to exist. To investigate the mechanisms underlying the inability of leptin to regulate food intake during early development, leptin signaling was analyzed both in vitro using primary cultures of rat embryonic ARC neurones and in vivo by challenging early postnatal rats with leptin. In neuronal cultures, despite the presence of key components of the leptin signaling pathway, no detectable activation of either signal transducer and activator of transcription 3 or the MAPK pathways by leptin was detected. However, leptin down-regulated mRNA levels of proopiomelanocortin and neuropeptide Y and decreased somatostatin secretion. Leptin challenge in vivo at postnatal d (P) 7, P14, P21, and P28 revealed that, in contrast to adult and P28 rats, mRNA levels of neuropeptide Y, proopiomelanocortin, agouti-related peptide and cocaine- and amphetamine-regulated transcript were largely unaffected at P7, P14, and P21. Furthermore, leptin stimulation increased the suppressor of cytokine signaling-3 mRNA levels at P14, P21, and P28 in several hypothalamic nuclei but not at P7, indicating that selective leptin insensitivity in the hypothalamus is coupled to developmental shifts in leptin receptor signaling. Thus, the present study defines the onset of leptin sensitivity in the regulation of energy homeostasis in the developing hypothalamus.
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PMID:Leptin sensitivity in the developing rat hypothalamus. 1787 66

Self-administration of ethanol and food share many common features and Richter hypothesized that an increase in ethanol consumption would decrease feeding to balance the excess calories contained in the ethanol. Previously, we have shown that individual alcohol consumption correlates with neurotransmitter gene expression, especially in the prefrontal cortex. To test the hypothesis of Richter, we measured hypothalamic gene expression of receptors or neuropeptides of known relevance for the regulation of food intake using qPCR and correlated this to individual ethanol consumption in Wistar rats. For validation, gene expression was first correlated with body weight. We found a correlation of dynorphin, somatostatin, melanocortin-4 receptor and serotonin 5-HT(2C) with body weight and trends to correlation for CART, thus confirming the established role of the hypothalamus in the regulation of weight. For ethanol consumption, correlations were found for CRH receptors 1 and 2 and vasopressin while strong trends were observed for galanin receptor 1, orexin receptor 1, MCH and adrenoceptor alpha(1B). Therefore, alcohol consumption does seem to involve several hypothalamic systems which also mediate feeding responses and suggests that the hypothalamus, together with the prefrontal cortex, may determine the 'stopping point' of an individual.
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PMID:The role of hypothalamic peptide gene expression in alcohol self-administration behavior. 1797 60

The protein fragment nesfatin-1 was recently implicated in the control of food intake. Central administration of this fragment results in anorexia and reduced body weight gain, whereas antisense or immunological nesfatin-1 antagonism causes increased food intake and overweight. Nesfatin-1 is derived from the precursor nucleobindin-2 (NUCB2). To identify the neurocircuitry underpinning the catabolic effects of NUCB2/nesfatin-1, we have used in situ hybridization and immunohistochemistry to map the distribution of this protein and its mRNA in the rat CNS and performed double-labeling experiments to localize its expression to functionally defined neuronal populations. These experiments confirm previous observations but also present several novel NUCB2 cell populations. Both NUCB2 mRNA and nesfatin-like immunoreactivity was most concentrated in the hypothalamus, in the supraoptic, paraventricular, periventricular and arcuate nuclei and the lateral hypothalamic area/perifornical region. Additionally, outside of the hypothalamus, labeling was observed in the thalamic parafascicular nucleus, the Edinger-Westphal nucleus, locus coeruleus, ventral raphe system, nucleus of solitary tract and in the preganglionic sympathetic intermediolateral cell column of the spinal cord, and the pituitary anterior and intermediate lobes. In neurons, immunoreactivity was almost exclusively confined to perikarya and primary dendrites with virtually no labeling of axonal terminals. Double-labeling immunohistochemistry revealed colocalization of nesfatin with vasopressin and oxytocin in magnocellular neuroendocrine neurons, thyrotropin-releasing hormone, corticotropin-releasing hormone, somatostatin, neurotensin, and growth-hormone-releasing hormone in parvocellular neuroendocrine neurons, pro-opiomelanocortin (but not neuropeptide Y) in the arcuate nucleus and melanin-concentrating hormone (but not hypocretin) in the lateral hypothalamus. Furthermore, nesfatin was extensively colocalized with cocaine- and amphetamine-regulated transcript in almost all NUCB2-expressing brain regions. These data reveal a wider distribution of NUCB2/nesfatin-1 than previously known, suggesting that the metabolic actions of this protein may involve not only feeding behavior but also endocrine and autonomic effects on energy expenditure. In addition, the subcellular distribution of nesfatin-like immunoreactivity indicates that this protein may not be processed like a conventional secreted neuromodulator.
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PMID:Distribution and neuropeptide coexistence of nucleobindin-2 mRNA/nesfatin-like immunoreactivity in the rat CNS. 1876 Oct 59

Enteric nerves harbour a wide array of neuropeptides playing a key role in the regulation of gastrointestinal tract functions. In this study, the distribution patterns of cocaine- and amphetamine-regulated transcript-immunoreactive (CART-IR) nerve fibres as well as the percentages of CART-positive enteric neurons were immunohistochemically assessed in the rumen, reticulum, omasum and abomasum of the sheep. Double staining were applied, to elucidate whether neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), somatostatin or serotonin co-exist in CART-IR gastric structures. In the rumen, reticulum, omasum and abomasum, a majority of myenteric neurons identified by immunoreactivity to Hu C/D were CART-positive (47.1 +/- 3.6%, 45.1 +/- 3.0%, 41.6 +/- 2.6% and 40.9 +/- 2.9% respectively). The smooth musculature of the forestomachs as well as abomasum was innervated with numerous CART-IR nerve fibres. Blood vessels-associated CART-positive nerve terminals were identified in the submucosa of the reticulum only. Lamina muscularis mucosae of the omasum and abomasum was moderately innervated with CART-IR nerve terminals. In the abomasum sparse CART-IR nerve fibres were seen between mucosal glands. A small population of endocrine cells of the abomasum also exhibited the presence of CART. All neuronal elements as well as endocrine cells IR to CART were negative to somatostatin and/or serotonin. No immunoreactivity to VIP, NPY and/or SP was found in myenteric ganglia-projecting CART-positive nerve fibres. The co-localization of CART with VIP, NPY and/or SP was regularly observed in myenteric neurons as well as the smooth muscle layer- and lamina muscularis mucosae-projecting nerve fibres. CART-IR nerve terminals located between mucosal glands of the abomasum frequently co-stored VIP, NPY and/or SP. Although the exact function of CART in the ovine forestomachs/stomach has to be elucidated, several potential functions (like enteric nerves protection) have been suggested.
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PMID:Immunodetection of cocaine- and amphetamine-regulated transcript in the rumen, reticulum, omasum and abomasum of the sheep. 1898 23

The distribution and morphology of neurons containing cocaine- and amphetamine-regulated transcript (CART) was investigated in the pig amygdala. CART- immunoreactive (CART-IR) cell bodies were rarely observed in the pig amygdala and most often they were present in the posterior (small-celled) parts of the basolateral and basomedial nuclei. In all other subdivisions only a small number of randomly scattered pericarya were present. In every region studied the CART-IR neurons formed a heterogeneous population consisting mostly of small, rounded or slightly elongated cell bodies, with a few poorly branched, smooth dendrites. In general, the morphological features of these cells clearly resembled non-pyramidal Golgi type II interneurons. Some randomly scattered CART-IR cell bodies were significantly larger and they demonstrated features of pyramidal-like Golgi type I projecting neurons. The highest densities of CART-IR fibres were evident within the central and medial nuclei. Moderate to high expression was found within the large-celled part of the basolateral nucleus and moderate to low levels in the lateral, basomedial and cortical nuclei. The routine double-labelling studies with antisera directed against CART and somatostatin (SOM), or neuropeptide Y (NPY), or cholecystokinin (CCK), or vasoactive intestinal peptide (VIP), or substance P (SP) demonstrated that, in general, these peptides do not co-exist in the CART-IR neurons. However, small subpopulations of the CART-IR fibres contained SOM, CCK, VIP or SP together.
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PMID:The cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in the amygdala of the pig. 2059 91


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