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)

Growth hormone (GH)-releasing peptides (GHRPs), a family of synthetic oligopeptides which stimulate GH release, were identified more than a decade ago. The effects of these peptides on GH release have been described in vivo and in vitro, in both animals and humans, using various doses and administration routes. It is generally accepted that GHRPs stimulate the release of GH by acting at the level of the pituitary through a receptor different to that for the endogenous GH-releasing hormone (GHRH). In addition, it has been reported that there are specific binding sites for these peptides in the hypothalamus and that systemic administration of GHRPs increases the expression of the immediate early gene c-fos in a subpopulation of hypothalamic neurons. However, the identity of these hypothalamic neurons and the mechanism of action of GHRPs at both the hypothalamic and pituitary levels remain unknown. One interesting aspect of GHRPs is that they are orally active and this phenomenon has been demonstrated in both animals and humans. Furthermore, these drugs stimulate GH secretion in humans dose-dependently with the magnitude and duration of this response being comparable to that seen with an intravenous peptide bolus. We have studied the oral activity of GHRP-2 on GH release in normal children. In addition, we have analyzed the response to GHRP-2 of obese adolescents, as well as the effects of an intravenous bolus of GHRH alone and GHRH plus GHRP-2. Orally administered GHRP-2 stimulates GH secretion in normal children and, although it seems that this drug is more potent in girls, there were no statistical differences between the groups. Characteristically, GH levels started to increase by 15 min, peaked at 60 min and returned to basal concentrations by 180 min. The effect of GHRP-2 was synergistic with GHRH 1-29 NH2. In addition, obese subjects appeared to have a greater response to this peptide than did normal controls. To study the effects of GHRPs on hypothalamic GHRH and somatostatin neurons, female dwarf rats (dw/dw) were treated continuously with GHRP-6 (1 mg/kg per 24 h) for 14 days. In situ hybridization for GHRH and SS was performed. We found that GHRP-6 stimulated GHRH mRNA levels in the posterior arcuate nucleus (ARC), with no significant effect in the anterior ARC or ventromedial hypothalamic neurons. SS mRNA levels in the posterior periventricular nucleus (PeN) were decreased after GHRP-6 treatment, while no effect was seen in the anterior PeN, ARC, or lateral paraventricular nucleus. These results suggest that GHRP-6 treatment modulates hypothalamic neurons controlling GH secretion; however, whether this effect is direct or mediated through another factor remains to be elucidated.
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PMID:Growth hormone-releasing peptides: clinical and basic aspects. 895 Jun 13

Changes in transcription factor and neuropeptide gene expression are likely to be involved in the cascade of genetic and molecular events leading to permanent changes in neuronal activity associated with kindling and epilepsy. Both acute-transient and delayed-sustained changes in transcription factor or immediate early gene (IEG) activity have previously been reported in response to different stimuli. In the present study in situ hybridization was used to investigate the possible time course (30 min-8 week) of IEG and neuropeptide mRNA induction in forebrain in a kindling model of epilepsy. Kindling was produced by daily unilateral stimulation of the amygdala. IEG mRNAs were detected using [35S]-labelled oligonucleotide probes specific for c-fos, c-jun, NGFI-A (PC1) and PC3 transcripts. Possible changes in the level of mRNAs encoding the neuropeptides somatostatin (SOM) and neuropeptide Y (NPY) were also studied. Stimulation-induced seizures produced dramatic bilateral increases in all IEG mRNAs in the dentate gyrus after 30 min to 1 h. Ipsilateral or bilateral increases in c-fos and PC3 mRNA were observed in the piriform cortex of individual animals at 30 min post-stimulation. While the distribution and apparent basal expression of the different IEGs varied (NGFI-A and c-jun > c-fos and PC3), the degree of induction in the dentate gyrus was similar for all IEGs studied (i.e. 200-300%). No long-term changes in IEG mRNA expression were detected beyond 2 h and up to 8 week after the last seizure. Increased levels of preproSOM and preproNPY mRNAs were consistently observed in hilar interneurons, but not in pyramidal or granule cells of the hippocampus, after 1-2 h. These increases were not maintained at later times. The short-term effects on IEG and neuropeptide mRNAs observed suggest that these changes are consequence of seizure activity with the development of kindling. In contrast, no evidence was found of any substantial, long-lasting effects on these parameters associated with the established kindled state.
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PMID:Rapid and transient increases in cellular immediate early gene and neuropeptide mRNAs in cortical and limbic areas after amygdaloid kindling seizures in the rat. 898 7

In this study we investigated the neurochemical identity of the arcuate cells activated following GH-releasing peptide-6 (GHRP-6) injection by comparing, on consecutive sections, the distribution c-fos messenger RNA (mRNA) with that of mRNAs for peptides synthesized in arcuate cells, including neuropeptide Y (NPY), GH-releasing factor (GRF), tyrosine hydroxylase, POMC, and somatostatin. Rats bearing chronically implanted jugular catheters were injected with either 50 micrograms GHRP-6 or vehicle. Thirty minutes later they were terminally anesthetized and perfused with fixative. Paraffin-embedded sections of 7 microns thickness were processed using in situ hybridization for either c-fos mRNA or mRNAs for the neurochemical markers. In GHRP-6-treated rats the mean (+/-SEM) number of cells expressing c-fos mRNA in the arcuate nucleus (23 +/- 2 cells/section per rat; n = 5) was significantly higher than for vehicle-treated controls (2 +/- 1 cells/section per rat; n = 5; P < 0.001, Mann-Whitney U test). Superimposed camera lucida maps indicated that, in GHRP-6-injected rats, neurochemically identifiable cells expressing c-fos mRNA also express NPY mRNA (51 +/- 4%), GRF mRNA (23 +/- 1%) tyrosine hydroxylase mRNA (11 +/- 3%), POMC mRNA (11 +/- 2%), or somatostatin mRNA (4 +/- 1%). Thus, the majority of cells expressing c-fos mRNA following GHRP-6 injection are NPY and GRF-containing cells.
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PMID:Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6. 900 14

The influence of morphine and somatostatin on nociceptor-evoked activation of central trigeminal neurons and cardiovascular reflex responses was assessed in barbiturate-anaesthetized rats. Morphine or the somatostatin analogue, octreotide, was given intracerebroventricularly 20 min prior to application of mustard oil to the corneal surface. The expression of the immediate early gene, c-fos, was used to estimate neuronal activation within the spinal trigeminal nucleus. Morphine reduced the number of Fos-positive neurons produced at the transition region between trigeminal subnucleus caudalis and the upper cervical spinal cord, whereas c-fos expression at the subnucleus interpolaris/caudalis transition was not affected significantly. Morphine also reduced the arterial pressure and heart rate responses to corneal stimulation in proportion to the dose of morphine and required a threshold dose similar to that which reduced c-fos expression. Naloxone prevented the morphine-induced inhibition of c-fos expression and cardiovascular reflex responses to corneal stimulation. Somatostatin analogue reduced the number of Fos-positive neurons at the subnucleus caudalis/cervical cord transition, but not at the subnucleus interpolaris/caudalis transition, an effect that was not prevented by naloxone. Somatostatin analogue did not blunt the cardiovascular responses evoked by corneal stimulation. A subthreshold dose of morphine plus a threshold dose of somatostatin analogue caused a greater inhibition of Fos-positive neurons at the subnucleus caudalis/cervical cord transition, but not in reflex-evoked autonomic responses, than the same dose of either drug alone. Intracerebroventricular administration of morphine and somatostatin analogue inhibit corneal activation of neurons within the superficial laminae at the subnucleus caudalis/cervical cord transition through opioid and non-opioid-dependent neural pathways, respectively. By contrast, the low sensitivity of corneal-responsive neurons at the subnucleus interpolaris/caudalis transition to analgesics suggests that these neurons are not simply a rostral extension of the medullary dorsal horn. Correlation analyses suggest that morphine-induced inhibition of cardiovascular responses to corneal stimulation depend on the activity of neurons at the subnucleus caudalis/cervical cord transition and not on those at the subnucleus interpolaris/caudalis transition region.
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PMID:Morphine and somatostatin analogue reduce c-fos expression in trigeminal subnucleus caudalis produced by corneal stimulation in the rat. 907 Jul 58

We reported previously that somatostatin inhibits the expression of the immediate early gene c-fos. Accordingly, we characterized the molecular mechanisms by which somatostatin inhibits c-fos gene expression. Because growth factors activate c-fos through a region of its promoter known as the serum response element [SRE; base pairs (bp) -357 to -276] we transfected rat pituitary adenoma cells (GH3) with plasmids containing the SRE or the SRE core fragment (bp -320 to -298) upstream of the luciferase reporter gene. Epidermal growth factor (EGF) stimulated SRE-luciferase activity, and this effect was inhibited by somatostatin and by the analog MK-678. Identical results were obtained with the SRE core plasmid, demonstrating that the sequence between bp -320 and -298 of the c-fos promoter is a somatostatin response element. Because the extracellular signal-regulated protein kinases (ERKs) induce the SRE via phosphorylation of transcription factors such as Elk-1, we examined the effect of somatostatin on ERK phosphorylation and activation. EGF stimulated tyrosine phosphorylation of ERK2, and MK-678 attenuated this effect. In experiments using in-gel kinase assays, MK-678 also inhibited EGF-stimulated ERK activity via a pertussis toxin sensitive pathway, and this effect resulted in inhibition of Elk-1 transcriptional activity. Our data suggest that one mechanism of somatostatin action involves inhibition of ERK activity, Elk-1 phosphorylation and transcriptional activation, and ultimately c-fos gene transcription.
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PMID:Molecular mechanisms for somatostatin inhibition of c-fos gene expression. 914 1

It has been surmised that GH exerts feedback action on the hypothalamus and thereby regulates its own secretion. Our previous studies suggested that GH acts on somatostatin neurons in the hypothalamic periventricular nucleus (PeV) and neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC). However, there remains uncertainty whether GH acts directly or indirectly through the generation of IGFs on the hypothalamus to regulate its own secretion. To examine this, rat GH (rGH) or human IGF-I was injected directly into a defined area of the hypothalamus, and the blood GH profile was observed in conscious male rats. In the rats given 0.5 microgram rGH into the ARC or PeV bilaterally, GH secretion was inhibited, and the inhibition lasted for 12 h. During the period of inhibition, the duration and amplitude of GH pulses were significantly decreased and the episodic secretion of GH appeared irregularly compared with the vehicle-injected control rats. In control rats given the vehicle or those given rGH into the lateral hypothalamus, the blood GH profile did not change and pulsatile GH secretion was produced every 3 h. When 0.1 microgram IGF-I was injected into the ARC or PeV bilaterally, the blood GH secretory pattern was not affected. Together with the results of our previous studies showing that c-fos gene expression was induced by systemic administration of GH and that GH receptor mRNA was contained in somatostatin neurons in the PeV and NPY neurons in the ARC, the data of the present study indicate that GH, but not IGF-I, acts on the cells in the ARC and the PeV or in their vicinity to inhibit its own secretion, presumably by activating the somatostatin and NPY neurons.
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PMID:Microinjection of rat GH but not human IGF-I into a defined area of the hypothalamus inhibits endogenous GH secretion in rats. 916 18

Activation of the cAMP pathway from the cell surface to the nucleus plays a major role in somatotroph differentiation and growth. This pathway is regulated mainly by the antagonistic hypothalamic hormones GHRH and somatostatin. Several pituitary-specific, as well as ubiquitous, expressed genes are regulated by cAMP in GH-secreting cells. Among them are the GH, GHF-1/Pit-1, c-fos and GHRH-receptor genes. Protein kinase A phosphorylation of Ser 133 of the transcription factor cAMP-responsive element binding protein (CREB), seems to play a pivotal role in the activation of the cAMP pathway in normal and tumoral somatotrophs. The oncogenic activating mutations of the G-protein as subunit stimulate transcription and CREB phosphorylation in somatotroph cells. The implications of the nuclear targets of cAMP in the differentiation and growth of somatotrophs are discussed in this review.
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PMID:Nuclear effects of the cAMP pathway activation in somatotrophs. 916 59

Somatostatin significantly suppressed cell growth of the mouse insulinoma-derived cell line MIN6. MIN6 cells exhibited high-affinity binding of somatostatin with 50% inhibitory concentration value of 0.9 nM. RNA blot analysis revealed that MIN6 cells expressed only SSTR3 among the five somatostatin receptors so far identified. Treatment of MIN6 cells with somatostatin significantly reduced the serum-induced c-fos expression levels. On the other hand, somatostatin (100 nM) treatment of MIN6 cells cultured in medium containing 10% serum transiently increased c-fos expression levels to 282 +/- 4.7% and then significantly decreased them to 27 +/- 7.6% of the levels before treatment. Mitogen-activated protein (MAP) kinase activity transiently increased to 656 +/- 91.2% and decreased thereafter to 39 +/- 13.3% of the activity before the addition of somatostatin (100 nM) into the medium. In addition, the stimulatory effect of somatostatin on c-fos expression and MAP kinase activity (early effect) was not altered by pertussis toxin (PTX), whereas the suppressive effect of somatostatin on c-fos expression and MAP kinase activity (late effect) was mitigated by PTX. These findings suggest that an inhibition of c-fos expression mediated by cross talk between PTX-sensitive G protein signaling and receptor tyrosine kinase signaling is one of the mechanisms by which somatostatin inhibits cell growth in MIN6 cells.
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PMID:Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin. 917 74

In addition to its role in olfaction and as a primary epileptogenic site, the anterior piriform cortex has been suggested to play a role in neuroperception of deficiencies or imbalances in physiologically essential amino acids. In recent studies, amino acid deficient diets were shown to induce expression of c-fos in the anterior piriform cortex within the rapid time frame associated with the normal anorectic response to such diets. It became important to examine the neurocytochemical architecture of this region for clues as to how and more precisely where dietary amino acid deficiency or imbalance might be monitored. The relationships of neuropeptide Y-, somatostatin-, and cholecystokinin-containing neurons were of particular interest because ongoing studies indicate that those peptides administered to the anterior piriform cortex alter intake of diets deficient in essential amino acids. The neuropeptides were endogenous to intrinsic neurons only; none resembled pyramidal projection neurons. Peptidergic neurons and fibers were concentrated most heavily in layer III of the paleocortex. The cytoarchitecture suggests that neuropeptide Y-, somatostatin-, and cholecystokin-containing neurons of the anterior piriform cortex may relate synaptically or multisynaptically to local circuit neurons during electrical activity, modulation of olfactory information, and neuroperception of essential amino acids.
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PMID:Neuropeptide Y, somatostatin, and cholecystokinin of the anterior piriform cortex. 918 99

To reveal neurones in the cat medulla oblongata involved in carotid baroreceptor/chemoreceptor reflexes, the distribution of c-Fos oncoprotein immunoreactivity was studied following electrical stimulation of the right carotid sinus nerve. The neurochemistry of the activated neurones was investigated using antisera to tyrosine hydroxylase, neuropeptide Y, somatostatin, and glutamate. Nitric oxide containing neurones were identified using antiserum to nitric oxide synthase (NOS) and by the histochemical localization of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase. Following sinus nerve stimulation numerous c-Fos-IR cells were detected both ipsilaterally and contralaterally in the nucleus tractus solitarii, the area postrema and throughout the ventrolateral medulla. Dual labelling studies revealed that 3.3% of c-Fos-immunoreactive cells in the nucleus tractus solitarii were also immunoreactive for tyrosine hydroxylase. The double labelled cells were scattered within the medial and ventrolateral subnuclei, predominantly rostral to obex. A higher proportion (10.3%) of c-Fos-IR cells in the ventrolateral medulla also showed tyrosine hydroxylase immunoreactivity. Caudal to obex, these were scattered in the reticular formation between the spinal trigeminal nucleus and the lateral reticular nucleus, while more rostrally they were found within the lateral reticular nucleus, the nucleus ambiguus and the lateral tegmental field. Cells expressing c-fos and reactive for glutamate, neuropeptide Y or NADPH-diaphorase (or NOS) were only rarely seen, and co-localization of c-Fos and somatostatin immunoreactivities was not seen. These results suggest that of the neurones forming pathways within the medulla activated on carotid sinus nerve stimulation, presumably mediating baro- and chemoreceptor reflexes, relatively few utilize catecholamines, glutamate, neuropeptide Y or nitric oxide as their transmitter substance.
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PMID:Co-localization of c-Fos and neurotransmitter immunoreactivities in the cat brain stem after carotid sinus nerve stimulation. 931 68


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