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)

Peripheral vasodilation initiates the hyperdynamic circulation in cirrhosis. Somatostatin and its analogues, such as octreotide, have a vasoconstrictive effect in cirrhotic patients and experimental animals with portal hypertension. The exact mechanism of octreotide-induced vasoconstriction remains unknown. To investigate whether octreotide produces vasoconstriction through suppression of vasodilatory peptides, such as glucagon, or through a local effect, we evaluated the effect of an intra-arterial dose on forearm blood flow (FBF), while measuring systemic glucagon levels. FBF was measured in 10 cirrhotic patients by venous occlusion plethysmography. The brachial artery of the nondominant arm was catheterized, and vasoactive drugs were administered: methacholine 4 microg/min; octreotide 20 microg/h, and octreotide 20 microg/h + methacholine 4 microg/min. Each infusion, lasting 5 minutes, was followed by saline for washout. FBF was measured in both arms during the last minute of each infusion and at the end of washout, with the uninfused arm acting as the control. Nitrates and nitrites, octreotide, and glucagon blood levels were determined at baseline and after each infusion. Percent change in flow (%triangle up) was obtained by comparing the flow during drug administration to that during the preceding saline infusion. Saline infusion did not alter FBF, but octreotide infusion resulted in a 34% +/- 7.7 (P <.005) reduction in FBF in the infused arm. FBF in the control arm was unchanged despite a significant decrease in systemic glucagon levels. Methacholine infusion increased FBF around 300%, which was not altered by the concomitant infusion of octreotide. Octreotide has a local vasoconstrictive effect that seems nitric oxide (NO)-independent. Octreotide probably has a facilitating effect over vasoconstrictors increased in chronic liver diseases.
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PMID:Local arterial vasoconstriction induced by octreotide in patients with cirrhosis. 1070 44

Whether nitric oxide (NO) plays a role in regulation of growth hormone (GH) secretion from somatotropes in the pituitary of the goldfish Carassius auratus was investigated. Immunocytochemistry with two antibodies against mammalian NO synthase (NOS) revealed the presence of a NOS-like enzyme in primary cultures of dispersed goldfish pituitary cells, including morphologically identified somatotropes. NO donors S-nitroso-N-acetylpenicillamine and sodium nitroprusside (SNP), as well as a cyclic guanosine monophosphate analogue (dibutyryl guanosine 3':5'-cyclic monophosphate), all significantly increased GH secretion from dispersed goldfish pituitary cells in static culture. Somatostatin abolished the response to SNP, and NOS inhibitors aminoguanadine hemisulfate (AGH) and N-(3-aminomethyl)benzylacetamidine, dihydrochloride (1400W) decreased the GH release response to known neuroendocrine factors stimulatory to GH release (gonadotropin-releasing hormone and a dopamine D1 agonist). AGH and 1400W did not alter basal GH secretion. These data suggest that NO plays a role in mediating the GH response to endogenous neuroendocrine factors in goldfish.
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PMID:Evidence that nitric oxide is involved in the regulation of growth hormone secretion in goldfish. 1084 97

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that may affect various functions of the CNS because the molecule and its receptors are expressed in the brain. The present study examines the effects of GM-CSF on sleep using rats and the secretion of three neurotransmitters/hormones that are involved in sleep regulation. When infused intracerebroventricularly at doses as low as 10 pmol for 10 hr during the dark period, GM-CSF promoted predominantly rapid eye movement (REM) sleep and moderate amounts of non-REM sleep without eliciting fever. An injection of GM-CSF (3.0 pmol) into the arcuate nucleus increased the release of nitric oxide (NO) from the hypothalamus but did not alter plasma levels of growth hormone. The release of somatostatin (SRIF) from the medial basal hypothalamus was stimulated by 1 x 10(-)(11) M GM-CSF. These findings indicated that centrally administered GM-CSF stimulates SRIF release through activation of the NO system in the hypothalamus. Because SRIF promotes REM sleep, it may also mediate the effects of GM-CSF on REM sleep. The present study indicates a novel central effect of GM-CSF that modulates sleep, supporting the notion that hematopoietic cytokines also play roles in the CNS.
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PMID:Granulocyte-macrophage colony-stimulating factor modulates rapid eye movement (REM) sleep and non-REM sleep in rats. 1088 38

Longitudinal muscle-myenteric plexus preparations of guinea pig intestines and sphincter of Oddi (SO) were immunostained for orphanin FQ/nociceptin. Orphanin FQ-immunoreactive (OFQ-IR) neurons and nerve fibers were relatively abundant in the SO, duodenum, ileum, cecum, and distal colon, with fewer neurons and nerve fibers observed in the proximal colon. Double staining with antibodies directed against the neuron-specific RNA binding protein Hu revealed that while the numbers of OFQ-IR neurons per ganglion decreased along the gut tube, similar proportions (7-9%) of neurons in these regions were OFQ-IR, whereas <1% of the neurons in the proximal colon were OFQ positive. In the ileum, where 8% of the myenteric neurons were OFQ-IR, all OFQ-IR neurons expressed choline acetyltransferase. In addition, multiple-label immunohistochemistry demonstrated that 58% of the OFQ-IR neurons were calretinin-IR, 52% were substance P-IR, and 28% were enkephalin-IR. Nitric oxide synthase immunoreactivity was observed in about 5% of OFQ-IR neurons, or 0.4% of the total population, and a similar proportion of the OFQ-IR neurons was positive for vasoactive intestinal peptide. No OFQ-IR neurons were immunoreactive for calbindin, somatostatin, or serotonin. These results, combined with previous studies of chemical coding and projection patterns in the guinea pig myenteric plexus, indicate that OFQ-IR is expressed preferentially in excitatory motor neurons projecting to the longitudinal and circular muscle layers, as well as a small subgroup of descending interneurons. Because OFQ is expressed by excitatory motor neurons, and because this peptide inhibits excitatory neurotransmission in the guinea pig ileum, it is likely that OFQ acts through a feedback autoinhibitory mechanism.
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PMID:Distribution and chemical coding of orphanin FQ/nociceptin-immunoreactive neurons in the myenteric plexus of guinea pig intestines and sphincter of Oddi. 1113 42

The ultrastructural features of neuronal nitric oxide synthase (NOS) -immunoreactive interneurons of rat nucleus accumbens shell and core were studied and compared. The NOS-containing subpopulation displayed characteristics similar to those previously described for nicotinamide adenine dinucleotide phosphate diaphorase-, neuropeptide Y, or somatostatin-containing striatal neurons, but also showed properties not previously associated with them, particularly the formation of both asymmetric and symmetric synaptic junctions. Inputs derived mainly from unlabeled terminals, but some contacts were made by NOS-immunolabeled terminals, by means of asymmetric synapses. Immunopositive endings that formed symmetric synapses were mainly onto dendritic shafts, whereas those that formed asymmetric synapses targeted spine heads. Morphometric analysis revealed that the core and shell NOS-stained neurons had subtly different innervation patterns and that immunostained terminals were significantly larger in the shell. A parallel investigation explored synaptic associations with dopaminergic innervation identified by labeling with an antibody against tyrosine hydroxylase (TH). In both shell and core, TH-positive boutons formed symmetric synapses onto NOS-containing dendrites, and in the core, TH- and NOS-immunolabeled terminals converged on both a single spiny dendrite and a spine. These results suggest that, in the rat nucleus accumbens, NOS-containing neurons may be further partitioned into subtypes, with differing connectivities in shell and core regions. These NOS-containing neurons may be influenced by a dopaminergic input. Recent studies suggest that nitric oxide potentiates dopamine release and the current study identifies the medium-sized, densely spiny neurons as a possible site of such an interaction.
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PMID:Ultrastructural features of the nitric oxide synthase-containing interneurons in the nucleus accumbens and their relationship with tyrosine hydroxylase-containing terminals. 1116 96

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

We recently described calbindin immunoreactivity in the myenteric plexus of the guinea-pig stomach. To study the neurochemical coding of calbindin D28 k (CALB)-containing myenteric neurones, the presence of calretinin (CALRET), choline acetyltransferase (ChAT), enkephalin (ENK), neuropeptide Y, serotonin (5-HT), somatostatin (SOM) and substance P(SP) was investigated immunohistochemically in colchicine-treated preparations. Nitric oxide synthase-containing neurones were detected by NADPH-diaphorase histochemistry. In addition, we investigated the neurone distribution patterns around the gastric corpus. Most CALB neurones were ChAT positive. ChAT/CALB neurones were either CALRET (ca 75%) or 5-HT positive and most contained in addition SP and/or ENK. All 5-HT neurones contained CALB. CALB labelled on average 2.3, 4.8 and 7.5 neurones per ganglion at the lesser curvature, in the central region and the greater curvature, respectively, which indicated a preferential localisation at the greater curvature. Compared to the total number of myenteric neurones, the proportion of CALB neurones increased significantly from the lesser curvature (6%) towards the greater curvature (18%). This shift, although observed for most ChAT/CALB-positive populations, was most prominent for the ChAT/CALB/CALRET/SP/ENK-encoded neurones. SOM-positive and ChAT-only encoded neurones were preferentially located at the lesser curvature. The remaining ten neurochemically defined populations did not exhibit an uneven distribution. The colocalisation of CALB with CALRET or 5-HT is specific for myenteric neurones in the stomach and represents one significant difference to the neurochemical code of CALB neurones in the guinea-pig intestine. The functional significance of the unevenness of neurone distribution along the circumference of the gastric corpus remains to be studied.
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PMID:Neurochemically distinct myenteric neurone populations containing calbindin have specific distribution patterns around the circumference of the gastric corpus. 1132 Jun 47

We analyzed the potential input and output components of nitric oxide synthase (NOS)-containing neurons in the rat superior colliculus (SC). To identify whether NOS-positive neurons receive glutamatergic input we investigated the colocalization of NOS with NMDA receptor subunit R1 (NMDAR1). In addition, to examine whether putative nitric oxide synthesizing neurons represent a neurochemically specific or distinct subpopulation of cells in the SC we studied the colocalization of NOS with the neurotransmitter GABA, the calcium-binding proteins parvalbumin, calbindin and calretinin and with neuropeptides such as somatostatin, substance P and neuropeptide Y. We found that 90% of NOS-positive neurons in the superficial layers of the rat SC express NMDAR1. Nearly 20% of the population of nitridergic neurons also expresses GABA and 15% of them express parvalbumin. NOS-positive neurons in the superior colliculus did not contain calretinin, calbindin or either of the neuropeptides tested. The results of this study show that the capacity for synthesizing NO in the SC is largely restricted to neurons that receive glutamatergic inputs and that some of these neurons express GABA or parvalbumin.
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PMID:Nitric oxide synthase-positive neurons in the rat superior colliculus: colocalization of NOS with NMDAR1 glutamate receptor, GABA, and parvalbumin. 1139 5

Recent studies have shown that somatostatin (SOM) inhibits interleukin 6 (IL-6) and interferon gamma (IFNgamma) production by lymphocytes and peritoneal macrophages, whereas substance P (SP) enhances these cytokines production. To define the mechanism of the cytokine production enhancements and inhibitions by SOM and SP, we examined the expression of apoptosis modulator, p53, Bcl-2, Bax, inducible nitric oxide synthase (iNOS), Fas, caspase-8 and nitric oxide (NO) in thioglycolate-elicited peritoneal macrophages. SOM caused up-regulation of p53, Bcl-2, Fas and caspase-8 activities, and down-regulation of iNOS expression and NO production. On the other hand, SP slightly induces p53 and highly induces Bcl-2, iNOS expression and NO production. These data suggest that apoptosis by SOM may occur by a Bax- and NO-independent p53 accumulation, and through Fas and caspase-8 activation pathways, and that the inducible expression of Bcl-2 and NO production by SP may contribute to prevent the signals of apoptosis by Bax, and via Fas and caspase-8 activation.
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PMID:Regulation of apoptosis by somatostatin and substance P in peritoneal macrophages. 1149 78

Neuronal nitric oxide-I is constitutively expressed in approximately 2% of cortical interneurons and is co-localized with gamma-amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal peroxynitrite, H(2)O(2)-formation and caspase activation.
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PMID:Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology. 1152 39


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