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 HCN-1A clonal cell line, derived from the cortical tissue of a patient with unilateral megencephaly, was shown to differentiate into a mature neuronal-like state in the presence of the nerve growth factor, dibutyryl cyclic adenosine, 3',5'-monophosphate and either 1-isobutyl-3-methylxanthine or forskolin. Differentiation was assessed by measuring the percentage of cells that displayed branched, varicose processes that stained for synaptophysin. Treatment of cultures with a cocktail containing forskolin increased immunocytochemical staining for gamma aminobutyric (GABA), neurofilament protein and the nerve growth factor receptor species p75NGFR. Treatment with acetyl-L-carnitine alone had some effects on the cell morphology while acetyl-L-carnitine arginyl amide and nerve growth factor together increased the GABA content. Positive staining levels for the neurotransmitters gamma aminobutyric acid, glutamate, somatostatin, cholecystokinin and vasoactive intestinal polypeptide were measured quantitatively for HCN-1A under basal conditions.
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PMID:Effects of nerve growth factor and acetyl-L-carnitine arginyl amide on the human neuronal line HCN-1A. 128 85

The level of expression of mRNAs encoding somatostatin and two isoforms of glutamic acid decarboxylase (Mr 65,000, GAD65 and 67,000, GAD67) was examined by quantitative in situ hybridization histochemistry in the striatum of adult rats after local injections of quinolinic acid. After a 2-week survival period, Nissl strains showed a profound loss of neurons in the injected striata. With a dose of 120 nmol quinolinic acid, the lesioned area was completely devoid of somatostatin mRNA-positive neurons but contained cells expressing nicotinamide adenine dinucleotide-diaphorase activity (a marker of somatostatinergic interneurons in striatum). After 60 nmol of quinolinic acid, the number of neurons expressing somatostatin mRNA in the lesioned area was similar to controls but the level of labeling per neuron was increased. In the lesioned area, labeling for GAD65 mRNA was abolished and labeling for GAD67 mRNA markedly reduced. However, scattered neurons expressing GAD67 mRNA could still be detected. The majority of surviving GABA-ergic neurons expressed immunoreactivity to parvalbumin, a marker for striatal GABA-ergic interneurons. The results show that quinolinic acid induces dose-dependent alterations in the expression of striatal somatostatin mRNA and reveal a relative sparing of GABA-ergic interneurons in the quinolinic acid-lesioned rat striatum.
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PMID:Effects of quinolinic acid on messenger RNAs encoding somatostatin and glutamic acid decarboxylases in the striatum of adult rats. 134 22

The electrical properties of neurones within the ventromedial hypothalamic nucleus of the rat were studied in an in vitro slice preparation, using conventional intracellular recording techniques. A detailed analysis of 36 intracellular recordings appeared to suggest 3 cell types, based on membrane capacitance and resistance characteristics, confirming previous reports of a diversity of cell types within this nucleus. The responsiveness of each cell type to exogenously-applied baclofen and somatostatin was also investigated. The inhibitory responses to both of these drugs were concentration-related (over the range 100 nM to 1 microM), tetrodotoxin-resistant and consisted of a membrane hyperpolarization (mean +/- SEM = 6.7 +/- 1 and 10.7 +/- 1 mV for 1 microM somatostatin and baclofen, respectively) and an associated reduction in the firing frequency of spontaneously active cells. These agonist-evoked responses probably represented direct postsynaptic actions but they were not restricted to any single type of cell. Evidence for an additional presynaptic effect of baclofen was also obtained. Responses to baclofen were extremely robust and readily quantifiable, whereas those to somatostatin showed pronounced long-lasting desensitization, which was particularly marked a larger concentrations. These data support previous contentions, based on in vivo studies, that somatostatin and GABA are likely to participate in the control of complex functions by the ventromedial hypothalamic nucleus.
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PMID:The effect of baclofen and somatostatin on neuronal activity in the rat ventromedial hypothalamic nucleus in vitro. 134 9

Corticotropin-releasing hormone (CRH), in addition to its neuroendocrine role, may act as a central neurotransmitter. Cerebral cortical CRH may have an important role in behavioral and neurodegenerative disorders. To gain an understanding of factors that may influence cortical CRH, we investigated the effect of several neurotransmitters and neuropeptides on the release of immunoreactive CRH (iCRH) from various cerebral cortical regions [frontal (FC), parietal (PC), temporal (TC), and occipital (OC)] in vitro. The hypothalamic release of iCRH was also evaluated under the same experimental conditions. Basal release of iCRH was approximately 2-fold, and KCl-stimulated iCRH release was approximately 4-fold higher in the hypothalamus than in any of the cortical regions. Cortical iCRH release was stimulated by 10 nM somatostatin (SRIF) in PC and 1 nM neuropeptide Y (NPY) in TC. Cortical iCRH release was inhibited by 1 and 10 nM acetylcholine (ACh), 0.1 microM glutamate, and 10 nM NPY. These effects were confined to the FC and/or PC. Hypothalamic iCRH release was stimulated by 1 and 10 nM ACh, 10 microM GABA, and 1 and 10 nM serotonin but was inhibited by 10 nM SRIF and 1 microM GABA. Growth hormone-releasing hormone did not affect cortical or hypothalamic iCRH release. These results demonstrate that CRH release from the cerebral cortex and the hypothalamus are under different regulatory mechanism(s). Furthermore, they indicate that the release of CRH in various cortical regions may be regulated differentially by the same neurotransmitter.
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PMID:Effect of various neurotransmitters and neuropeptides on the release of corticotropin-releasing hormone from the rat cortex in vitro. 135 Jan 13

Glutamate and GABA content in different regions of adult female rat brain were determined at 10 and 30 min following intraventricular injection of LHRH or somatostatin. Cerebral cortex, cerebellar and hypothalamic glutamate levels were significantly elevated at 30 min following injection of 1 micrograms somatostatin, whereas hypothalamic glutamate levels were elevated at 10 min following a 0.5 micrograms dose. LHRH at a dose of 1 micrograms elevated cerebellar and brain stem glutamate levels at 10 and 30 min, whereas a 0.5 micrograms dose significantly elevated cerebral cortex, cerebellar and hypothalamic glutamate levels at 30 min. Third ventricular injection of 1 micrograms somatostatin produced a significant decrease in hypothalamic GABA levels at 10 and 30 min, whereas a 0.5-microgram dose decreased brain stem GABA levels at 10 min. LHRH at a dose of 0.1 microgram significantly increased cerebral cortex and cerebellar GABA levels at 10 min and brain stem GABA levels at 10 and 30 min following injection. Intraventricular injection of LHRH at a dose of 0.5 microgram significantly elevated cerebral cortex, cerebellar and brain stem GABA levels at 30 min. Hypothalamic GABA levels were elevated at 10 and 30 min following 0.5 and 1 microgram intraventricular LHRH injection. The implications of these results are discussed in relation to probable interaction between these neuroactive amino acids and neuropeptides in the rat brain.
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PMID:Acute and short-term effects of intraventricular injection of somatostatin and LHRH on glutamate and GABA levels in rat brain. 135 1

The aim of this work was the identification of pharmacologically distinct subtypes of gamma-aminobutyric acidB (GABAB) receptors in the central nervous system. Inasmuch as GABAB receptors are often sited on axon terminals where they mediate inhibition of transmitter release, we chose as models the GABAB receptors mediating inhibition of release of 1) endogenous GABA; 2) endogenous glutamate; and 3) somatostatin-like immunoreactivity (SRIF-LI). The experimental set up consisted of rat cerebrocortical synaptosomes depolarized in superfusion with 12 or 15 mM KCl. Endogenous GABA and glutamate were measured by high-performance liquid chromatography and SRIF-LI by radioimmunoassay. The selective GABAB receptor agonist (-)-baclofen inhibited in a concentration-dependent manner the K(+)-evoked release of GABA, glutamate and SRIF-Ll with similar potencies and efficacies [EC50 values, 1.1-1.5 microM; maximal inhibition, 45-50% at about 10 microM (-)-baclofen]. The GABAB receptor antagonist phaclofen concentration-dependently reduced the effects of (-)-baclofen on the release of GABA and SRIF-Ll but not on the release of glutamate, where it was ineffective up to 1000 microM. The rank order of potency (Ki values are shown in parentheses) are: SRIF-Ll (7.8 microM); GABA (10.4 microM); and glutamate (greater than 115 microM). The novel GABAB receptor antagonist 3-aminopropyl(diethoxymethyl) phosphinic acid (CGP 35348) displayed a different pattern on the three release systems examined (Ki values are shown in parentheses): SRIF-Ll (0.38 microM); glutamate (0.48 microM); and endogenous GABA (greater than 115 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional evidence for multiple gamma-aminobutyric acidB receptor subtypes in the rat cerebral cortex. 135 47

Progestin receptor-containing cells in the hypothalamus of the adult female green monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical methods to determine their anatomical location, neurotransmitter content and afferent connections. Animals were ovariectomized and administered either estradiol valerate or the oil injection vehicle, and were sacrificed after 10 days of treatment. Using a monoclonal antibody raised against rabbit uterine progestin receptor (PR), the distribution of PR-immunoreactive cells in the mediobasal hypothalamus and the effect of estrogen treatment on this distribution was determined. PR-immunoreactive cells were found throughout the ventromedial nucleus (VMN), in the area between the VMN and fornix, and in the medial portion of the infundibular nucleus. Estrogen treatment dramatically increased both the number of labeled cells and the intensity of immunoreaction product in these regions. In double-immunostained sections, boutons immunoreactive for antigens indicative of serotonin, pro-opiomelanocortin derived peptides, GABA, catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin were demonstrated to establish synaptic contact with the soma of PR-immunoreactive hypothalamic neurons. In colchicine-pretreated animals, all PR-containing neurons in the mediobasal hypothalamus were found to contain immunoreactivity for glutamic acid decarboxylase, the enzyme required for synthesis of GABA. No evidence of colocalization with other antigens, including LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic innervation PR-containing GABAergic cells may represent steroid-sensitive sites of integration for inputs from other neural systems involved in the control of gonadotropin secretion.
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PMID:Transmitter content and afferent connections of estrogen-sensitive progestin receptor-containing neurons in the primate hypothalamus. 135 61

The effects of GABAergic influences intrinsic to the hypothalamus on the secretion of somatostatin were studied using cultured fetal rat hypothalamic neurons. The existence of GABAergic neurons within the cultures was confirmed by immunocytochemistry. These neurons appeared to be actively secreting GABA as antagonism of GABAA receptors with bicuculline and picrotoxinin caused a dose-dependent increase in the release of immunoreactive somatostatin (SRIF), which was Ca(2+)-dependent. Although exogenous GABA inhibited SRIF secretion at concentrations of 10(-6) M and greater, muscimol, a GABAA agonist, inhibited SRIF release at 10(-8) M, whereas baclofen, a GABAB agonist, required concentrations two orders of magnitude greater to produce an effect. Phaclofen, a GABAB antagonist, was inactive (10(-8)-10(-4) M). A GABA uptake inhibitor, SKF 89976A, produced a dose-dependent inhibition of SRIF release. These results, therefore, support a role for intrahypothalamic GABA neurons in the regulation of SRIF secretion in the neonatal rat, predominantly via a type A receptor, and provide further evidence for a neuroendocrine role for GABA in controlling growth hormone secretion.
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PMID:GABAergic influences on somatostatin secretion from hypothalamic neurons cultured in defined medium. 135 34

The influence of sustained epileptic seizures evoked by intraperitoneal injection of kainic acid on the gene expression of the neuropeptides somatostatin and neuropeptide Y and on the damage of neurons containing these peptides was studied in the rat brain. Injection of kainic acid induced an extensive loss of somatostatin and, though less pronounced, of neuropeptide Y neurons in the inner part of the hilus of the dentate gyrus. Neuropeptide Y-immunoreactive neurons located in the subgranular layer of the hilus, presumably pyramidal-shaped basket cells, were spared by the treatment. Although neuropeptide Y messenger RNA was not detected in granule cells of control rats, it was found there after kainic acid seizures at all time intervals investigated (12 h to 90 days after injection of kainic acid). High concentrations of neuropeptide Y messenger RNA were especially observed 24 h after injection of kainic acid. At this time neuropeptide Y messenger RNA was also transiently observed in CA1 pyramidal cells. Neuropeptide Y synthesis in granule cells in turn gave rise to an intense immunoreactivity of the peptide in the terminal field of mossy fibers which persisted for the entire time period (90 days) investigated. In addition, neuropeptide Y messenger RNA concentrations were also drastically elevated in presumptive basket cells located at the inner surface of the granule cell layer, especially at the "late" time intervals investigated (30-90 days after kainic acid). These data support the concept that extensive activation of granule cells by limbic seizures contributes to the observed neuronal cell death in CA3 pyramidal neurons and interneurons of the hilus. Consecutively, basket cells containing neuropeptide Y and presumably GABA might be activated and participate in recurrent inhibition of granule cells. Neuropeptide Y-immunoreactive fibers observed in the inner molecular layer at "late" time intervals after kainic acid may result either from collateral sprouting of mossy fibers or from basket cells extensively expressing the peptide. It is speculated that neuropeptide Y synthesized and released at a high rate from granule cells and basket cells may exert a protective action against seizures.
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PMID:Functional changes in neuropeptide Y- and somatostatin-containing neurons induced by limbic seizures in the rat. 136 Jan 55

The development of GABAergic interneurons in feline striate area and extrastriate areas was tracked by single and double labeling immunohistochemistry using antibodies to GABA and to molecular markers which identify subpopulations of GABAergic neurons in adult mammalian neocortex; i.e., neuropeptide Y, somatostatin, and the calcium-binding proteins parvalbumin and calbindin. The density of GABA-ir neurons was relatively constant during development and among visual areas. By contrast, most of the GABA-subpopulations increased in the cortex of visual areas during postnatal development, and thus the proportion of GABA-ir neurons which also expressed another molecular marker increased during development. By the end of the first postnatal month, the neurotransmitter phenotypes of the neocortical GABAergic neurons are mature.
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PMID:Development of subpopulations of GABAergic neurons in cat visual cortical areas. 149 19


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