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)

By combining a Drosophila genome data base search and reverse transcriptase-PCR-based cDNA isolation, two G-protein-coupled receptors were cloned, which are the closest known invertebrate homologs of the mammalian opioid/somatostatin receptors. However, when functionally expressed in Xenopus oocytes by injection of Drosophila orphan receptor RNAs together with a coexpressed potassium channel, neither receptor was activated by known mammalian agonists. By applying a reverse pharmacological approach, the physiological ligands were isolated from peptide extracts from adult flies and larvae. Edman sequencing and mass spectrometry of the purified ligands revealed two decapentapeptides, which differ only by an N-terminal pyroglutamate/glutamine. The peptides align to a hormone precursor sequence of the Drosophila genome data base and are almost identical to allatostatin C from Manduca sexta. Both receptors were activated by the synthetic peptides irrespective of the N-terminal modification. Site-directed mutagenesis of a residue in transmembrane region 3 and the loop between transmembrane regions 6 and 7 affect ligand binding, as previously described for somatostatin receptors. The two receptor genes each containing three exons and transcribed in opposite directions are separated by 80 kb with no other genes predicted between. Localization of receptor transcripts identifies a role of the new transmitter system in visual information processing as well as endocrine regulation.
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PMID:Functional annotation of two orphan G-protein-coupled receptors, Drostar1 and -2, from Drosophila melanogaster and their ligands by reverse pharmacology. 1216 55

The goal of this study was to elucidate the anti-convulsion mechanisms of ear-point stimulation in rat with experimental seizure. We prepared the epilepsy rats by intrahippocampal injection of penicillin. One hour later the lower 1/2 auricular lobules of seizure rats, containing ear-points Pizhixia and Shenmen etc., was electrically stimulated, which was imitated as ear-point electrical acupuncture in humans. Radioimmunoassay and biochemical techniques were used to determine the contents of somatostatin and amino acid neurotransmitters in hippocampus of rats. The outcomes revealed epileptiform behaviors of rat were appeared after penicillin-injected. The contents of somatostatin, aspartic acid, glutamine and GABA were increased. When these rats were subsequently given the ear-point electrical stimulation, the convulsion behaviors were definitely improved. At the same time the contents of the somatostatin, aspartic acid and glutamine in hippocampus of seizure rat were significantly decreased correspondingly. The contents of glycine, taurine and GABA had increased. Based on the results above, it was suggestive that ear-point electrical stimulation had anti-epilepsy effects, which might be involved in the decreases of the contents of the somatostatin, aspartic acid and glutamine, and increases of the contents of glycine, taurine and GABA in hippocampus of seizure rat.
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PMID:The effects of ear-point stimulation on the contents of somatostatin and Amino acid neurotransmitters in brain of rat with experimental seizure. 1538 88

Inflammatory bowel syndrome (IBS) mainly includes ulcerative colitis (UC) and Crohn's disease (CD). UC and CD are chronic and recurrent conditions, with a tendency to exacerbations and remissions. The incidence of diseases worldwide has increased over the last years. Although the etiology of inflammatory bowel syndrome has been studied intensively it still remains unclear. The development and persistence of inflammation is an effect of numerous factors: proinflammatory (aggressive), regulating bowel mucosa homeostasis and protective factors. Proinflammatory factors include intestinal bacteria, bile acids, digestive enzymes, lipopolysaccharides and peptidoglycans. Protective mechanisms are impermeability of mucosa barrier, presence of intestinal mucus, activity of secretive immunoglobulins, some prostaglandins and interleukins, glutamine, somatostatin, cortisol and short-chain fatty acids. Factors modifying intestinal mucosa homeostasis consist of genetically determined immunoregulators and activity of intestinal mucosa barrier and some environmental factors (diet, smoking, infections, stress, antibiotics and others). Environmental factors are jointly responsible for IBS occurrence in case of genetically determined dysregulation leading to proinflammatory cytokines overproduction or disturbances in synthesis of cytokines regulating intestinal mucosa homeostasis.
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PMID:[Environmental factors in the etiopathology of inflammatory bowel syndrome]. 1555 1

Mechanisms by which gut luminal content regulates secretion and motility are ill understood. We evaluated whether neuroendocrine enterochromaffin (EC) cells act as luminal sensors for a wide variety of nutrients and defined the secretory mechanisms of this process. Pure (98-99%) FACS-sorted human EC cells and neoplastic EC cells (KRJ-I) were studied. RT-PCR identified transcripts for T2R1 (bitter), OR1G1 (class II olfactory) and trace amine (TAR1) G protein-coupled receptors (GPCRs) and transporters for glutamine (SNAT1/2), glucose (GLUT1/3/SGLT1), and bile salts (ABST). Glutamine and sodium deoxycholate stimulated 5-HT release (EC(50) = 0.002-0.2 microM; 2-fold release) but were 10-100 times more potent in neoplastic EC cells, which also secreted 6-13 times more 5-HT. Tastants (caffeine, tyramine, octopamine) and olfactants (thymol and eugenol) also stimulated normal and neoplastic EC cell 5-HT secretion (EC(50) = 1.2 nM to 2.1 microM and 0.05 nM to 0.1 microM release, respectively); 2-deoxyglucose and the artificial sweetener sucralose also stimulated (EC(50) = 9.2 and 0.38 nM). 5-HT release was associated with ERK phosphorylation (1.5-fold, P < 0.02) and could be inhibited by a somatostatin analog (IC(50) = 1 pM). Eleven secretory associated genes including the vesicle docking inhibitor STXBP3 were upregulated in response to glutamine and bile salt stimulation in neoplastic EC cells. Targeting STXBP3 expression by use of antisense knockdown significantly (P < 0.05) reduced 5-HT secretion. In conclusion, EC cells express GPCRs and transporters for luminal tastants, olfactants, glutamine, glucose, and bile salts. Activation includes a panel of secretory genes, ERK phosphorylation, and 5-HT secretion. Luminal EC cell regulation is likely to be as important as G cell regulation in gastric acid secretion; development of agents to target EC cell function is therefore a critical therapeutic goal.
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PMID:Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. 1855 22

L-glutamate, the main excitatory neurotransmitter, influences virtually all neurones of the neuroendocrine hypothalamus via synaptic mechanisms. Vesicular glutamate transporters (VGLUT1-3), which selectively accumulate L-glutamate into synaptic vesicles, provide markers with which to visualise glutamatergic neurones in histological preparations; excitatory neurones in the endocrine hypothalamus synthesise the VGLUT2 isoform. Results of recent dual-label in situ hybridisation studies indicate that glutamatergic neurones in the preoptic area and the hypothalamic paraventricular, supraoptic and periventricular nuclei include parvocellular and magnocellular neurosecretory neurones which secrete peptide neurohormones into the bloodstream to regulate endocrine functions. Neurosecretory terminals of GnRH, TRH, CRF-, somatostatin-, oxytocin- and vasopressin-secreting neurones contain VGLUT2 immunoreactivity, suggesting the co-release of glutamate with hypophysiotrophic peptides. The presence of VGLUT2 also indicates glutamate secretion from non-neuronal endocrine cells, including gonadotrophs and thyrotrophs of the anterior pituitary. Results of in vitro studies show that ionotropic glutamate receptor analogues can elicit hormone secretion at neuroendocrine/endocrine release sites. Structural constituents of the median eminence, adenohypophysis and neurohypophysis contain elements of glutamatergic transmission, including glutamate receptors and enzymes of the glutamate/glutamine cycle. The synthesis of VGLUT2 exhibits robust up-regulation in response to certain endocrine challenges, indicating that altered glutamatergic signalling may represent an important adaptive mechanism. This review article discusses the newly emerged non-synaptic role of glutamate in neuroendocrine and endocrine communication.
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PMID:Novel aspects of glutamatergic signalling in the neuroendocrine system. 1860 97


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