Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to further investigate our postulate regarding the inhibitory role played by central alpha 2-adrenergic pathways on hypothalamic somatostatin (SS) release in rats. The growth hormone (GH) responses to exogenous GH-releasing factor (GRF; 3 micrograms/kg i.v.) or clonidine (CLO; 100 micrograms/kg i.v.), either given alone or in combination, were tested in 3-month-old male rats made GH-releasing hormone (GH-RH) deficient neonatally by administration of monosodium glutamate (MSG; 4 mg/g body weight s.c.). To prevent the presumable decrease in the pituitary GH content in these animals from leading to an erroneous interpretation of the results obtained, half of these rats were given GRF (MSG-GRF rats; 30 micrograms/kg s.c.) for 3 days immediately prior to GH testing. The other half of MSG-treated and non MSG-treated rats received saline during these days (MSG-S and controls, respectively). To establish the efficiency of GRF priming, the pituitary GH content was measured in other MSG-GRF, MSG-S, and control animals. The mean (+/- SEM) GH peaks in response to GRF challenge were significantly higher in controls than in MSG-GRF rats (125.2 +/- 28.5 vs. 67.5 +/- 19.4 micrograms/l; p < 0.05), while no significant GRF-induced GH release was observed in the MSG-S group. Most likely these results are related to the different pituitary GH content, significantly (p < 0.01) higher in controls than in MSG-GRF rats, and in the latter higher than in MSG-S animals (p < 0.05). CLO administration did not evoke a significant GH release in MSG rats, whether primed with GRF or not.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Clonidine potentiates the growth hormone response to a growth hormone releasing hormone challenge in hypothalamic growth hormone releasing hormone deficient rats. 761 33

N-Methyl-D-aspartate (NMDA) receptors are enriched in the neostriatum and are thought to mediate several actions of glutamate including neuronal excitability, long-term synaptic plasticity, and excitotoxic injury. NMDA receptors are assembled from several subunits (NMDAR1, NMDAR2A-D) encoded by five genes; alternative splicing gives rise to eight isoforms of subunit NMDAR1. We studied the expression of NMDA receptor subunits in neurochemically identified striatal neurons of adult rats by in situ hybridization histochemistry using a double-labeling technique. Enkephalin-positive projection neurons, somatostatin-positive interneurons, and cholinergic interneurons each have distinct NMDA receptor subunit phenotypes. Both populations of striatal interneurons examined express lower levels of NMDAR1 and NMDAR2B subunit mRNA than enkephalin-positive neurons. The three striatal cell populations differ also in the presence of markers for alternatively spliced regions of NMDAR1, suggesting that interneurons preferentially express NMDAR1 splice forms lacking one (cholinergic neurons) or both (somatostatin-positive neurons) alternatively spliced carboxy-terminal regions. In addition, somatostatin- and cholinergic-, but not enkephalin-positive neurons express NMDAR2D mRNA. Thus, these striatal cell populations express different NMDAR-subunit mRNA phenotypes and therefore are likely to display NMDA channels with distinct pharmacological and physiological properties. Differences in NMDA receptor expression may contribute to the relative resistance of striatal interneurons to the neurotoxic effect of NMDA receptor agonists.
...
PMID:NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum. 762 52

In 1987, 25 years after the synthesis of the potent and selective GABAB agonist baclofen (1), Kerr et al. described the first GABAB antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABAB antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABAB antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABAB receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABAB antagonists interacted also with postsynaptic GABAB receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABAB antagonists showed also protective effects in various animal models of absence epilepsy.
...
PMID:Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. 765 Jun 85

Glutamate sensitivity development and interactions of somatostatin (SRIF) with AMPA/Kainate receptor-mediated glutamate responses were studied in dissociated hypothalamic neurons from 16-day-old mouse embryos grown in vitro. Only 18% of functionally innervated cells could be found at 6-9 DIV whereas the percentage of innervated neurons progressively increased thereafter to reach 100% at 19-22 DIV. The glutamate sensitivity, estimated from glutamate-induced peak inward current, was very low at 6-9 DIV, sharply increased at 11-14 DIV and developed at a low increase rate thereafter. SRIF either unaffected glutamate peak current (27% of the cells), or significantly decreased (50%) or increased it (23%). Pertussis Toxin pretreatment abolished the SRIF-induced decrease of the glutamate response without affecting the excitatory effect. The number of glutamate responsive neurons inhibited by SRIF increased with time in culture whereas that of neurons responding to SRIF by an increased glutamate response was not statistically modified by functional innervation. The present data suggest that increased glutamate sensitivity coincides with the onset of functional synaptogenesis in mouse hypothalamic neurons in culture. SRIF can modulate glutamate sensitivity of hypothalamic neurons with either synergistic or antagonistic effects. Since glutamate has been shown to stimulate SRIF synthesis and secretion from hypothalamic neurons, the reverse capacity of SRIF to modulate the glutamate response suggests that both transmitters exhibit complex reciprocal interactions.
...
PMID:Modulation by somatostatin of glutamate sensitivity during development of mouse hypothalamic neurons in vitro. 765 5

The segmental and laminar origin of propriospinal antinociceptive systems in the cat spinal cord and the modes to activate them are characterized. The experiments were performed on pentobarbital-anesthetized cats with a high cervical spinalization. Recordings were made from single lumbar spinal dorsal horn neurons responding to noxious radiant skin heating and to innocuous mechanical skin stimuli. The segmental and laminar origin of heterosegmental, propriospinal neurons modulating background activity and nociceptive responses were identified and the conditions to activate them were characterized. Conditioning noxious front paw stimulation and superfusion of the cervical enlargement with L-glutamate, but not with substance P, reduced noxious heat-evoked responses of about 50% of all lumbar neurons tested. Glutamate superfusions of the lower thoracic or upper sacral spinal cord enhanced background activity and reduced nociceptive responses of most lumbar spinal dorsal horn neurons. Superfusions with substance P or somatostatin were ineffective. Glutamate microinjections into the superficial layers of the thoracic, upper lumbar or sacral dorsal horn ipsi- or contralateral to the recording sites or into lamina VIII of the ipsilateral thoracic or upper lumbar cord reduced noxious heat-evoked responses with or without changes in the level of background activity. It is concluded that propriospinal neurons originating from circumscribed areas of the cervical, thoracic, lumbar or sacral spinal cord independently modulate background activity and noxious heat-evoked responses of multireceptive lumbar spinal dorsal horn neurons. The incidence and efficacy of propriospinal antinociceptive stimulation sites was found to be as high as for the classical region of endogenous antinociception, the midbrain periaqueductal gray.
...
PMID:Characteristics of propriospinal modulation of nociceptive lumbar spinal dorsal horn neurons in the cat. 768 6

An impairment of energy metabolism may underlie slow excitotoxic neuronal death in neurodegenerative diseases. We therefore examined the effects of intrastriatal, subacute systemic, or chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in rats. Following intrastriatal injection 3-NP produced dose-dependent striatal lesions. Neurochemical and histologic evaluation showed that markers of both spiny projection neurons (GABA, substance P, calbindin) and aspiny interneurons (somatostatin, neuropeptide Y, NADPH-diaphorase) were equally affected. Subacute systemic administration of 3-NP produced age-dependent bilateral striatal lesions with a similar neurochemical profile. However, in contrast to the intrastriatal injections, striatal dopaminergic afferent projections were spared. Both freeze-clamp measurements and chemical shift magnetic resonance spectroscopy showed that 3-NP impairs energy metabolism in the striatum in vivo. Microdialysis showed no increase in extracellular glutamate concentrations after systemic administration of 3-NP. The lesions produced by intrastriatal injection or systemic administration of 3-NP were blocked by prior decortication. However, the NMDA antagonist MK-801 did not block the effects of intrastriatal 3-NP, consistent with a non-NMDA excitotoxic mechanism. In contrast to subacute systemic administration of 3-NP, chronic (1 month) administration produced lesions confined to the striatum in which there was relative sparing of NADPH-diaphorase interneurons, consistent with an NMDA excitotoxic process. Chronic administration showed growth-related proliferative changes in dendrites of spiny neurons similar to changes in Huntington's disease (HD). These results are consistent with in vitro studies showing that mild metabolic compromise can selectively activate NMDA receptors while more severe compromise activates both NMDA and non-NMDA receptors. Chronic administration of 3-NP over 1 month produces selective striatal lesions that replicate many of the characteristic histologic and neurochemical features of HD.
...
PMID:Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. 769 9

Continuous cerebral cortical cell lines have been developed from two patients, an 11-month-old with unilateral megalencephaly and a seven-year-old with Rasmussen's encephalitis, designated HCN-1 and HCN-2, respectively. The two cell lines stain for neuronal markers such as neurofilament and neuron-specific enolase but not for non-neuronal markers such as glial fibrillary acidic protein and S-100 protein. In the presence of appropriate growth factors, the cells extend long, branched processes resembling neurons. Differentiation of HCN-1 cells can be induced with nerve growth factor, dibutyryl cyclic AMP and isobutylmethylxanthine, while for HCN-2 cells nerve growth factor, isobutylmethylxanthine and the phorbol ester 12-O-tetradecaoylphorbol-13-acetate are most effective. Immunohistochemical staining of both differentiated cell lines reveals intense staining for GABA, glutamate, somatostatin, cholecystokinin-8 and methionine enkephalin. Two human cortical neuronal cell lines have been developed which represent neuronal precursors. These cell lines propagate in culture and are capable of differentiating upon the addition of a variety of growth factors and chemical agents. These cell lines should prove to be useful models for the study of in vitro neuronal processes.
...
PMID:Human cerebral cortical cell lines from patients with unilateral megalencephaly and Rasmussen's encephalitis. 770 May 10

Metabotropic glutamate receptors (mGluRs) mediate the effects of glutamate neurotransmission on intracellular second messenger systems. Among the seven distinct mGluR receptor isoforms currently identified, the mGluR5 isoform is expressed particularly prominently in the striatum, where it may contribute to neuronal plasticity, motor behaviors, and excitotoxic injury. mGluR5 mRNA expression in striatal enkephalinergic, somatostatinergic, and cholinergic neurons was examined using double label in situ hybridization techniques. mGluR5 expression is abundant in a large number of medium-sized striatal cells but is absent in a significant minority of neurons. Double label in situ hybridization with 35S-dATP- and digoxygenin-dUTP-tailed oligonucleotide probes demonstrated that mGluR5 message is highly expressed by enkephalinergic striatal neurons but is not detectable in cholinergic or somatostatin interneurons. In addition, some nonenkephalin, presumably substance P, neurons were also strongly labeled for mGluR5. The differential expression of mGluR5 in striatal projection neurons vs. interneurons may contribute to the selective vulnerability of these neurons to disease processes.
...
PMID:Differential expression of mGluR5 metabotropic glutamate receptor mRNA by rat striatal neurons. 778 1

Pharmacological doses of growth hormone (GH) in humans and rats increase plasma and muscle glutamine values. As major surgery results in a physiological rise in serum GH concentration, we investigated whether this physiological increase in GH altered glutamine metabolism. Eighteen patients undergoing coronary artery bypass graft (CABG) surgery were randomly assigned to receive somatostatin, 100 micrograms subcutaneously at induction of anaesthesia and 8 hourly for 48 h, or placebo. Somatostatin effectively blocked the physiological surge of GH following injury but did not affect plasma or muscle glutamine concentrations, which fell significantly in both groups. Plasma glutamine decreased by 31% (P < 0.01) and 28% (P < 0.01) in the control and somatostatin groups respectively. Muscle glutamine was reduced 45% (P < 0.001) in the control group and 50% (P < 0.001) in the somatostatin group. There was no difference in muscle or circulating glutamate, alanine or branched chain amino acid concentrations or in metabolite values between the somatostatin-treated patients and the control group. There was no relationship between the GH response to surgery and glutamine metabolism following major surgery.
...
PMID:Growth hormone suppression and glutamine flux associated with cardiac surgery. 782 Sep 81

GABAA receptors mediate the inhibition of somatostatin gene expression and NMDA receptors mediate its stimulation. The aim of this study was to determine whether the two major neurotransmitters in the central nervous system (GABA and glutamate) could interact to control somatostatin mRNA content in primary cultures of hypothalamic neurons. Neurons were incubated for 15 min on days 3, 5, 7 or 11 of culture with Mg(2+)-free medium containing either NMDA (20 microM) or bicuculline (50 microM) to investigate the ontogenesis of somatostatin somatostatin secretion in response to NMDA and GABA. We found that NMDA significantly elicited somatostatin release from day 3, and bicuculline-induced release was observed from day 5. An ontogenetic study of somatostatin mRNA levels revealed that it steadily increased up to day 5 (6-fold) and a slight but nonsignificant decrease was observed on day 7 which stabilized until day 13. Experiments were thus carried out on day 11 of culture. Pharmacological manipulations of the two types of receptors (NMDA and GABAA) were performed to study the effect of the interaction on somatostatin mRNA accumulation. Time-course studies revealed the optimal time of action of the neurotransmitters (20 h). Our results demonstrated that bicuculline-induced mRNA accumulation was not additive with that elicited by NMDA after 20 h of incubation. In contrast, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d')cyclohepten-5,10-imine hydrogen (MK-801) at 10 microM completely abolished the stimulatory effect of bucuculline during the same time period. In addition, muscimol was unable to decrease somatostatin mRNA levels when NMDA receptors were blocked by MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:GABAA and NMDA receptor activation controls somatostatin messenger RNA expression in primary cultures of hypothalamic neurons. 784 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---