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 localization of gamma-aminobutyric acid (GABA) high-affinity binding sites was investigated in the exocrine and endocrine pancreas of neonatal rats by means of 3H-GABA autoradiography. GABA-binding was identified on Schwann cells and on the cells of the intralobular excretory ducts. In the endocrine part of the pancreas, no labelling was observed except in peripheral islet cells which, on the basis of their scarcity and distribution, could be somatostatin cells. Furthermore, peri-insular innervation showed considerable labelling.
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PMID:Localization of GABA high-affinity binding sites in the pancreas of neonatal rat. 671 82

Under control conditions, superfused slices of the dorsal half of the lumbar enlargement from adult rats released Met-enkephalin-like material (MELM) that behaved as authentic Met-enkephalin under two different chromatographic procedures (Bio-gel filtration, HPLC). MELM release increased markedly on exposure of slices to batrachotoxin (0.5 microM) or to an excess of K+ (28 and 56 mM instead of 5.6 mM). The K+-evoked release was totally dependent on the presence of Ca2+ in the superfusing fluid whereas the spontaneous efflux of MELM was only partially Ca2+-dependent. Further experiments performed with tissues of polyarthritic rats indicated that the increase in their MELM levels was associated with a lower fractional rate constant of MELM release, therefore suggesting that spinal Met-enkephalin turnover might be reduced in chronically suffering animals. Examination of the possible modulation of MELM release by various neuroactive compounds present within the dorsal horn revealed that cholecystokinin (10 microM), but not its desulphated derivative, substance P-sulphoxide (10 microM), and to a lesser extent substance P, enhanced the K+-evoked MELM release. In contrast, gamma-aminobutyric acid (10 microM) and (-)-baclofen (1 microM) partially prevented the stimulatory effect of K+ on MELM release. Other compounds such as serotonin, somatostatin, and neurotensin altered neither the spontaneous nor the K+-evoked release of MELM.
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PMID:Basic and regulatory mechanisms of in vitro release of Met-enkephalin from the dorsal zone of the rat spinal cord. 674 33

Increasing the levels of endogenous gamma-aminobutyric acid (GABA) by treating rats with GABA-transaminase inhibitors (ethanolamine-O-sulphate and gamma acetylenic GABA) resulted in a decrease in plasma levels of GH. Diminishing GABAergic activity by inhibiting GABA synthesis with 3-mercaptopropionic acid or by blocking GABA receptors with bicuculline increased plasma concentration of GH. The presence of GABA was without effect on the basal, somatostatin-inhibited or high K+-stimulated secretion of GH by hemipituitary glands in vitro. The results suggest that GABA inhibits secretion of GH under the given experimental circumstances.
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PMID:Possible inhibitory influence of gamma-aminobutyric acid on growth hormone secretion in the rat. 732 70

Several ion channels can be regulated by G proteins in a "membrane-delimited" manner. The cardiac muscarinic K+ (KACh) channel, which is responsible for the acetylcholine (ACh) or adenosine-induced deceleration of heart beat and atrioventricular conduction, is the prototype of this type of receptor-dependent regulation of ion channels. Because similar transduction mechanisms are utilized by various membrane receptors, such as somatostatin, 5-hydroxytryptamine-1, alpha 2-adrenergic, mu-and delta-opioid, D2-dopamine, and gamma-aminobutyric acid B receptors, in neuronal, hormone-secreting, renal, or smooth muscle cells, the G protein (GK)-KACh channel system illustrates the principles underlying one of the most important cell signaling mechanisms (B. Hille. Neuron 9: 187-195, 1992). It seems that both alpha- and beta gamma-subunits of GK may be involved in the regulation of the KACh channel of mammalian atrial muscle. A general consensus of opinion has emerged, after some years of controversy, to support the notion that physiological activation of the channel by GK is the responsibility of the beta gamma-subunits. Recent evidence suggests that the KACh channel interacts with the alpha-subunit in the terminating process of activation.
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PMID:G protein regulation of cardiac muscarinic potassium channel. 748 49

Gastropancreatic neuroendocrine cells synthesize large amounts of gamma-aminobutyric acid (GABA). This amino acid neurotransmitter appears to be stored in and released from, vesicles similar to small synaptic vesicles. So far, the function of GABA in gastropancreatic, neuroendocrine cells has not been clarified. Previous work suggested that only pancreatic, glucagon-producing alpha 2 cells contain functional GABAA receptors. Using subunit-specific antibodies in sections of human antral mucosa, a human gastrinoma and rat pancreas, we show that expression of GABAA receptors is abundant in gastropancreatic, neuroendocrine cells. Using the patch-clamp technique in the whole-cell mode we demonstrate that both the rat insulinoma cell line RIN 38 and the amphicrine cell line AR42J express functional GABAA receptors, which are characterized by a relatively low benzodiazepine and Zn2+ sensitivity and by an insensitivity to the inverse benzodiazepine agonist 6,7-alpha-methoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). In contrast to neurons, activation of GABAA receptors leads to a membrane depolarization. This depolarization presumably activates voltage-gated Ca2+ channels, resulting in an increase in cytosolic Ca2+ concentration, [Ca2+]i, as shown with the fluorimetric dye fura-2. The combination of GABA release, GABAA receptor activation and the [Ca2+]i increase could constitute an autocrine mechanism, modulating the release of hormones such as gastrin, insulin and somatostatin.
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PMID:Expression of functional GABAA receptors in neuroendocrine gastropancreatic cells. 749 Dec 62

The mechanism of periodic gonadotropin-releasing hormone (GnRH) secretion from hypothalamic neurons is difficult to elucidate due to the diffuse distribution of GnRH neurons and the complex interaction of neuronal inputs onto them. Recent use of transgenic techniques allowed construction of an immortalized GnRH neuronal cell line (GT1), which has neuronal markers and secretes GnRH in a periodic fashion. Using the patch-clamp recording technique in the whole-cell and nystatin perforated-patch configuration, the present experiments show that this cell line expressed a tetrodotoxin-sensitive Na channel, two types of Ca channels, three types of outward K channels and a K inward rectifier. The latter current was suppressed in some cells by GnRH or somatostatin. In addition, a gamma-aminobutyric acid (GABA) response, presumably through GABAA receptors, is recorded. In long-term current-clamp recordings, spontaneous depolarizing activity was found to increase, and then decrease, between 20-35 min after removal of the cells from serum- and steroid-containing medium. In some cases, more than one cycle of activity was seen. Under voltage clamp, an inward current was recorded at similar times, with reversal at about -15 mV. Thus, two mechanisms of cell interaction, GABAA responses and feedback through GnRH responses, and one mechanism of endogenous periodic electrical activity were observed in these cells, which could synchronize periodic GnRH release.
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PMID:Ion channel properties and episodic activity in isolated immortalized gonadotropin-releasing hormone (GnRH) neurons. 750 28

AR42J cells derive from azaserine-induced malignant nodules from the rat pancreas. They differ from normal acinar cells for at least three reasons: 1) they proliferate rapidly; 2) they synthesize, store, and secrete digestive enzymes but the regulation of their exocrine function is abnormal, from the emergence of atypical receptors (e.g., cholecystokinin octapeptide type B and pituitary adenylate cyclase-activating polypeptide type I receptors) to unusual inositol phosphate metabolism and cytoskeleton disorganization; and 3) they possess an added neuroendocrine-regulated pathway characterized by voltage-sensitive ionic currents, post-translational processing of peptidic prohormones (and possibly autocriny), and the release of small neurotransmitters (gamma-aminobutyric acid, glycine, and glutamic acid). These amphicrine cells represent, therefore, a cancerous version of the primordial pancreatic ductular epithelium. Dexamethasone favors their differentiation toward the exocrine phenotype. The mitogenic pathway is favored by the occupancy of receptor tyrosine kinases, adenosine 3',5'-cyclic monophosphate, ornithine decarboxylase expression, and Na(+)-H+ exchange. Somatostatin opposes proliferation through protein phosphatases.
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PMID:Pancreatic tumoral cell line AR42J: an amphicrine model. 751 39

In a double-blind, placebo-controlled trial, the effects of recombinant human growth hormone were studied on cerebrospinal fluid concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), monoamine metabolites, neuropeptides and endogenous opioid peptides. Twenty patients, 10 patients in each of 2 groups, with adult-onset, growth hormone deficiency were treated for 1 month with recombinant human growth hormone (0.25 U/kg/week) or placebo. All the patients received the appropriate thyroid, adrenal and gonadal hormone replacement. In cerebrospinal fluid, the mean concentration of growth hormone increased from 13.3 +/- 4.4 to 149.3 +/- 22.2 muU/l (p = 0.002), during recombinant human growth hormone treatment. The cerebrospinal fluid IGF-I concentration increased from 0.67 +/- 0.04 to 0.99 +/- 0.10 micrograms/l (p = 0.005) and the IGFBP-3 concentration rose from 13.4 +/- 1.25 to 17.5 +/- 1.83 micrograms/l (p = 0.002). The dopamine metabolite homovanillic acid decreased from 282.1 +/- 36.0 to 234.3 +/- 26.5 nmol/l (p = 0.02) and the vasoactive intestinal peptide decreased from 4.1 +/- 0.6 to 3.7 +/- 0.4 pmol/l (p = 0.03). Cerebrospinal fluid immunoreactive beta-endorphin increased from 24.4 +/- 1.8 to 29.9 +/- 2.1 pmol/l (p = 0.002). There were no significant changes compared to baseline in the cerebrospinal fluid concentrations of enkephalins, dynorphin A, the norepinephrine metabolite 3-methoxy-4-hydroxyphenyl-ethyleneglycol, the serotonin metabolite 5-hydroxyindoleacetic acid, gamma-aminobutyric acid, somatostatin or corticotropin-releasing factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters. 753 55

The seemingly contradictory observations in previous publications that gamma-aminobutyric acid (GABA) is detected in all cell bodies of the suprachiasmatic nucleus (SCN) and that terminals originating from the SCN are only 20-30% GABA positive prompted us to investigate whether this might be explained by a preference of colocalization in terminals of certain peptidergic neurons in the SCN or by a day/night rhythm in GABA synthesis. At three different circadian times, animals were perfusion fixed, and their SCNs were stained for vasopressin (VP), somatostatin (SOM), or vasoactive intestinal polypeptide (VIP). Subsequently, the number of GABA peptide-positive terminals was determined using GABA postembedding staining in ultrathin sections. It appeared that the highest percentage of colocalization with GABA was detected in VIP terminals (38%) and the lowest in VP terminals (15%). No differences in colocalization percentages could be observed in any parameter at any circadian time. In the dorsomedial hypothalamus, one of the target areas of the VP and VIP fibers from the SCN, a colocalization of GABA within VP and VIP terminals was found similar to that in the SCN. In the region of the somatostatin-containing neurons in the SCN, a number of axoaxonal contacts could be observed that sometimes exhibited synaptic specializations. In nearly all cases, the axoaxonic terminals contained GABA and/or SOM. The conclusion is that the high level of intrinsic GABAergic connections in the SCN represents a putatively powerful mechanism to synchronize or shut down the activity of the SCN. We discuss the possibility that, depending on the firing frequency of the neurons, the colocalization of GABA with all peptides under investigation allows for the selection of which transmitter is released, the peptidergic one or the amino acid.
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PMID:Colocalization of gamma-aminobutyric acid with vasopressin, vasoactive intestinal peptide, and somatostatin in the rat suprachiasmatic nucleus. 756 Feb 91

This study was undertaken in order to establish the presence of pluripotential neuroblasts in the developing chick CNS. This has been suggested by our previous observations that expression of emerging neuronal phenotypes in the chick embryo CNS is affected by exposure to neurotrophic substances (i.e., GHRH, SRIF, NGF, EGF, muscle-derived factors) or neurotoxins such as ethanol. We have proposed that one mechanism whereby these substances elicit their effects is by shifting phenotypic expression in populations of pluripotential neuroblasts. In order to establish the presence of significant populations of pluripotential neuroblasts, cultures obtained from 3-day-old whole chick embryos (E3WE) were double-stained with antibodies to markers specific for four neuronal phenotypes in various permutations. Cultures at 6 DIV were tested for the presence of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), gamma-aminobutyric acid (GABA), and somatostatin (SRIF) alone, and in various combinations. We observed a colocalization of all phenotypic markers within neuronal perikarya and processes in more than fifty percent of neuronal cells in these cultures. These data suggest that developing neuroblasts at this stage of embryogenesis possess the machinery necessary to adopt multiple neuronal phenotypes. The colocalization of neurotransmitter proteins in early neuroblasts (60 hr of embryogenesis) supports the recent concept that these substances themselves may influence phenotypic expression and also supports our idea that microenvironmental factors (i.e., ethanol, growth factors) provide signals which affect emerging phenotypes.
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PMID:Early neuroblasts are pluripotential: colocalization of neurotransmitters and neuropeptides. 756 50


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