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

During infection, bacterial and viral products, such as bacterial lipopolysaccharide (LPS), cause the release of cytokines from immune cells. These cytokines can reach the brain by several routes. Furthermore, cytokines, such as interleukin-1 (IL-1), are induced in neurons within the brain by systemic injection of LPS. These cytokines determine the pattern of hypothalamic-pituitary secretion that characterizes infection. IL-2, by stimulation of cholinergic neurons, activates neural nitric oxide synthase (nNOS). The nitric oxide (NO) released diffuses into corticotropin-releasing hormone (CRH)-secreting neurons and releases CRH. IL-2 also acts in the pituitary to stimulate adrenocorticotropic hormone (ACTH) secretion. On the other hand, IL-1 alpha blocks the NO-induced release of luteinizing hormone-releasing hormone (LHRH) from LHRH neurons, thereby blocking pulsatile LH but not follicle-stimulating hormone (FSH) release and also inhibiting sex behavior that is induced by LHRH. IL-1 alpha and granulocyte macrophage colony-stimulating factor (GMCSF) block the response of the LHRH terminals to NO. The mechanism of action of GMCSF to inhibit LHRH release is as follows. It acts on its receptors on gamma-aminobutyric acid (GABA)ergic neurons to stimulate GABA release. GABA acts on GABAa receptors on the LHRH neuronal terminal to block NOergic stimulation of LHRH release. IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH-releasing hormone (GHRH) release, which is mediated by NO, and stimulating somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of PRL release is also mediated by intrahypothlamic action of NO, which inhibits release of the PRL-inhibiting hormone dopamine. The actions of NO are brought about by its combined activation of guanylate cyclase-liberating cyclic guanosine monophosphate (cGMP) and activation of cyclooxygenase (COX) and lipoxygenase (LOX) with liberation of prostaglandin E2 and leukotrienes, respectively. Thus, NO plays a key role in inducing the changes in release of hypothalamic peptides induced in infection by cytokines. Cytokines, such as IL-1 beta, also act in the anterior pituitary gland, at least in part via induction of inducible NOS. The NO produced inhibits release of ACTH. The adipocyte hormone leptin, a member of the cytokine family, has largely opposite actions to those of the proinflammatory cytokines, stimulating the release of FSHRF and LHRH from the hypothalamus and FSH and LH from the pituitary directly by NO.
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PMID:The mechanism of action of cytokines to control the release of hypothalamic and pituitary hormones in infection. 1126 67

Parvalbumin-containing fast-spiking interneurons in the cerebral cortex exhibit widespread electrical coupling, as do somatostatin-containing low-threshold spiking interneurons. Besides the classical neurotransmitter gamma-aminobutyric acid, these cortical interneurons may also release various neuropeptides including substance P (SP), as well as the freely diffusible messenger nitric oxide (NO). To investigate whether these two networks of interneurons might interact via these nonclassical messengers, we performed immunocytochemistry for SP and NO signaling pathways in rat somatic sensory cortex. SP was found in a subset of parvalbumin-positive cells concentrated in layers IV and V, whereas its receptor, NK1, was found in a subset of somatostatin-containing neurons (and also, at much lower levels, in a disjoint subset of parvalbumin-containing neurons). Only 4% of SP-containing axon terminals were apposed to NK1-positive dendrites, suggesting that in the cerebral cortex, SP may act predominantly as a paracrine neuromediator. Nitric oxide synthase-I (NOS-I), the synthetic enzyme for NO, was found almost exclusively in NK1-positive neurons; 95% of intensely somatostatin/NK1-positive neurons were also positive for NOS-I, and 94% of NOS-positive neurons were also positive for NK1. Immunoreactivity for soluble guanylyl cyclase (the NO receptor) was at high levels in the apical dendrites of layer V pyramidal neurons and in parvalbumin/SP-positive neurons. These data point to a novel reciprocal chemical interaction between two inhibitory networks in the rat neocortex.
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PMID:Substance P and nitric oxide signaling in cerebral cortex: anatomical evidence for reciprocal signaling between two classes of interneurons. 1174 51

Although the composition of the gastric innervation has been determined in animal models, relatively little known about the innervation of the human antro-pyloric region. We used immunocytochemical techniques to establish the localization and co-expression of neuropeptides and nitric oxide in the human antrum and upper duodenum. Our results demonstrate the existence of a clearly defined submucosal plexus in the antral region that is absent in rats and guinea pigs. The abundant innervation of the lamina propria contains 3 major nerve populations: VIP- and NOS-, SP- and CGRP-, and GRP-immunoreactive. For the first time, NOS-containing nerve fibers were observed throughout the length of the antral glands. Within the antrum somatostatin was confined to endocrine cells, however, at the pyloric sphincter both enteric plexi contained immunoreactive neurons and nerve fibres. Within the pyloric sphincter CGRP- and SP-immunoreactive fibres were significantly increased, correlating with the presence of large ganglia in the submucosal plexus. In conclusion, the organization and composition of the innervation of human antro-pylorus differed substantially from that reported in other mammals. The presence of an abundant mucosal innervation paralled by a well-defined submucosal plexus indicates that the functional regulation of the gastric-pyloric region will be distinct from that of smaller animal models.
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PMID:The innervation of the human antro-pyloric region: organization and composition. 1176 92

Using altitude hypoxia model, in situ hybridization and NADPH-d histochemistry, we investigated the effects of ketamine and L-NAME (blocker of NOS) on NOS and somatostatin mRNA (SS mRNA) expression in the rat hypothalamus following acute altitude hypoxia. It was revealed that acute altitude hypoxia induced NOS and SS mRNA overexpression in the rat hypothalamus. When pretreated with NMDA receptor antagonist ketamine and L-NAME, NOS and SS mRNA expression were inhibited significantly. These results suggest that NMDA receptor activation participates in the expression of NOS and SS mRNA in the rat hypothalamus subjected to acute altitude hypoxia. Meanwhile, hypothalamic endogenous NO may mediate expression of SS mRNA.
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PMID:[Ketamine and L-NAME inhibit NOS and somatostatin mRNA expression induced by altitude hypoxia in the rat hypothalamus]. 1196 80

Somatostatin receptors (SSTRs) have been identified in most hormone-producing tumors as well as in breast cancer. In the present study, we determined SSTR1-5 expression in primary ductal NOS breast tumors through semi-quantitative RT-PCR and immunocytochemistry. The results from the analysis of 98 samples were correlated with several key histological markers and receptor expression. All five SSTR subtypes are variably expressed at the mRNA level in breast tumors with 91% of samples showing SSTR1, 98% SSTR2, 96% SSTR3, 76% SSTR4, and 54% SSTR5. SSTR1-5 are localized to both tumor cells and the surrounding peritumoral regions as detected by immunocytochemistry. Levels of SSTR mRNA, when corrected for beta-actin levels, were highest for SSTR3 followed by SSTR1, SSTR2, SSTR5, and SSTR4. Furthermore, there was good correlation between mRNA and protein expression with 84% for SSTR1, 79% for SSTR2, 89% for SSTR3, 68% for SSTR4, 68% for SSTR5, and 78% for all five receptors. SSTR1, 2 and 4 were correlated with ER levels whereas SSTR2 showed an additional correlation with PR levels. These correlations were independent of patient age and histological grade. Moreover, using immunocytochemistry, blood vessels exhibited receptor-specific localization for SSTR2 and SSTR5. Our results indicate significant correlations between mRNA and protein expression along with receptor-specific correlations with histological markers as well as ER and PR levels. Differential distribution of SSTR subtypes in tumors and receptor-specific expression in vascular structures may be considered as a novel diagnosis for breast tumors with receptor subtype agonists.
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PMID:Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1--5 and correlation with receptor protein expression and tumor pathology. 1598 28

The distribution of somatostatin and cocaine and amphetamine-regulated transcript (CART) was investigated in rat intracardiac ganglia. Somatostatin immunoreactivity was only present in nerve terminals, always colocalised with choline acetyltransferase immunoreactivity, surrounding approximately 10% of intracardiac neurons. Somatostatin-immunoreactive terminals particularly targeted intrinsic cardiac neurons that were immunoreactive for calbindin. Somatostatin was also present in sympathetic cholinergic neurons in the stellate ganglia, but could not be detected in neurons of the nucleus ambiguus and dorsal motor nucleus of the vagus in the brainstem. CART immunoreactivity was present in 46% of intracardiac neuronal somata, including those that expressed either NOS or calbindin immunoreactivity but was never present in terminals forming pericellular baskets around intracardiac neurons. CART immunoreactivity was absent from sympathetic cell bodies in the stellate ganglia, but was present in nerve terminals around sympathetic neurons. Based on the results of this study, additional chemical diversity was identified among elements of the rat cardiac nervous system that may define neural pathways of different function.
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PMID:Cocaine- and amphetamine-related transcript peptide and somatostatin in rat intracardiac ganglia. 1637 20

Microcysts are most evident in the posteroventral and anteroventral cochlear nuclei (PVCN and AVCN) of the Mongolian gerbil. The origin and contents of the microcyst are not elucidated at present. The present study investigated the possible inclusions in the microcyst by employing immunocytochemical labeling to localize the existence of various protein markers. Thirty and 100 microm thick sections were used to substitute and reconstruct between 6 and 20 paraffin serial sections, respectively. In 30-microm-thick slice sections, immunoreactivity of glial fibrillary acidic protein (GFAP-IR), mitochondria inner membrane (MCA-In-IR), S-100 (S-100-IR), serotonin (5-HT-IR), myelin proteolipid protein (PLP-IR) and substance P (SP-IR) abutted on the perimeter of the microcyst. The immunolabeled SP-positive cells were adjacent to the evagination of the microcyst. In 100-microm-thick slice sections, immunoreactivity of nitric oxide synthase (NOS-IR) and somatostatin (SOM-IR) mainly precipitated as flocculent structures in the small to medium-sized microcysts. 5-HT-IR also precipitated as an elongated flocculent stalk adjacent to the large microcyst or randomly distributed in the neuropil. The findings suggest that GFAP, MCA-In, S-100, 5-HT, PLP, SP, NOS and SOM may be involved in modulating the physiological functions and maintaining micro-environmental homeostasis of the microcyst in the cochlear nucleus of the gerbil.
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PMID:Protein markers in the microcyst of the posteroventral cochlear nucleus of the gerbil. 1795 57

Biotechnology has enabled greater understanding of the cellular and molecular biology of acute pancreatitis and has offered the possibility of a new generation of biodrugs to treat this disease. The proteases inhibitor gabexate mesilate has proven to be effective for endoscopic retrograde cholangiopancreatography-induced pancreatitis but, given the low incidence of this condition, its cost-effectiveness has to be evaluated. Randomised controlled trials have shown no benefit for somatostatin or its analogue octreotide although some practitioners continue to use it to prevent organ damage and complicated disease. Antioxidant therapy has been thoroughly investigated in animal models but the results of large scale clinical trials are awaited. The use of kinin inhibitors is in its infancy and has not yet reached the clinic. Considerable interest has been engendered in nitric oxide (NO), firstly for its beneficial use in acute lung injury resulting from the multi-organ failure of acute pancreatitis and secondly, the possible benefits of NOS inhibition to prevent pancreatitic necrosis. Tumour necrosis factor antagonism and interleukin- 1 blockade are 2 therapies awaiting clinical trials because there is overwhelming evidence of their benefit in animal models. Interleukin-10, an anticytokine, may have similar benefits and has been shown to be beneficial in animal models when given as pretreatment. The only biodrug that has progressed to phase III clinical trials is the platelet-activating factor antagonist lexipafant. Successful phase II studies have been followed up by a phase III study indicating benefits in reduction of organ failure and pseudocyst formation and reduction in mortality when treatment is given within 48 hours of onset of the disease. Finally, prophylactic therapy with selected antibacterials in patients with predicted severe disease can reduce local complications and possibly mortality.
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PMID:Acute pancreatitis: an overview of emerging pharmacotherapy. 1802 Jun 8

In addition to the well-characterized direct and indirect projection neurons there are four major interneuron types in the striatum. Three contain GABA and either parvalbumin, calretinin or NOS/NPY/somatostatin. The fourth is cholinergic. It might be assumed that dissociated cell cultures of striatum (typically from embryonic day E18.5 in rat and E14.5 for mouse) contain each of these neuronal types. However, in dissociated rat striatal (caudate/putamen, CPu) cultures arguably the most important interneuron, the giant aspiny cholinergic neuron, is not present. When dissociated striatal neurons from E14.5 Sprague-Dawley rats were mixed with those from E18.5 rats, combined cultures from these two gestational periods yielded surviving cholinergic interneurons and representative populations of the other interneuron types at 5 weeks in vitro. Neurons from E12.5 CD-1 mice were combined with CPu neurons from E14.5 mice and the characteristics of striatal interneurons after 5 weeks in vitro were determined. All four major classes of interneurons were identified in these cultures as well as rare tyrosine hydroxylase positive interneurons. However, E14.5 mouse CPu cultures contained relatively few cholinergic interneurons rather than the nearly total absence seen in the rat. A later dissection day (E16.5) was required to obtain mouse CPu cultures totally lacking the cholinergic interneuron. We show that these cultures generated from two gestational age cells have much more nearly normal proportions of interneurons than the more common organotypic cultures of striatum. Interneurons are generated from both ages of embryos except for the cholinergic interneurons that originate from the medial ganglionic eminence of younger embryos. Study of these cultures should more accurately reflect neuronal processing as it occurs in the striatum in vivo. Furthermore, these results reveal a procedure for parallel culture of striatum and cholinergic depleted striatum that can be used to examine the function of the cholinergic interneuron in striatal networks.
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PMID:Striatal interneurons in dissociated cell culture. 2049 May 35

Intrinsic choroidal neurons (ICNs) exist in some primates and bird species. They may act on both vascular and non-vascular smooth muscle cells, potentially influencing choroidal blood flow. Here, we report on the chemical coding of ICNs and eye-related cranial ganglia in the chicken, an important model in myopia research, and further to determine synaptic input onto ICN. Chicken choroid, ciliary, superior cervical, pterygopalatine, and trigeminal ganglia were prepared for double or triple immunohistochemistry of calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT), dopamine-beta-hydroxylase, galanin (GAL), neuronal nitric oxide synthase (nNOS), somatostatin (SOM), tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), vesicular monoamine-transporter 2 (VMAT2), and alpha-smooth muscle actin. For documentation, light, fluorescence, and confocal laser scanning microscopy were used. Chicken ICNs express nNOS/VIP/GAL and do not express ChAT and SOM. ICNs are approached by TH/VMAT2-, CGRP-, and ChAT-positive nerve fibers. About 50% of the pterygopalatine ganglion neurons and about 9% of the superior cervical ganglion neurons share the same chemical code as ICN. SOM-positive neurons in the ciliary ganglion are GAL/NOS negative. CGRP-positive neurons in the trigeminal ganglion lack GAL/SOM. The neurochemical phenotype and synaptic input of ICNs in chicken resemble that of other bird and primate species. Because ICNs lack cholinergic markers, they cannot be readily incorporated into current concepts of the autonomic nervous system. The data obtained provide the basis for the interpretation of future functional experiments to clarify the role of these cells in achieving ocular homeostasis.
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PMID:Intrinsic choroidal neurons in the chicken eye: chemical coding and synaptic input. 2060 73


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