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)

Immunohistochemistry of peptide- and dopamine-beta-hydroxylase-(DBH)-containing varicose nerve fibres and ganglion cells, respectively, in the guinea pig inferior mesenteric ganglion was investigated following a) transsection of mesenteric (colonic) branches, b) transsection of central (lumbar splanchnic, intermesenteric and hypogastric) branches, and c) transplantation into the spleen. The findings indicate that pathways of different opioid peptides are not identical. Met-enkephalin- and met-enkephalin-arg-phe- (cleavage products from pre-proenkephalin) containing fibres course in central branches to make contact in the inferior mesenteric ganglion. Dynorphin- and alpha-neo-endorphin- (deriving from pre-prodynorphin) containing fibres as well as leu-enkephalin- (included in the dynorphin sequence) fibres appear to rise not only from central and from enteric somata, but also from intraganglionic noradrenergic neurons. Similar pathways seem to be used by VIP- and by neurotensin-immunoreactive fibres, although intraganglionic neurotensin-immunoreactive cell bodies are rare. Practically all substance P- and most CGRP-immunoreactive fibres enter the ganglion via central branches and, to a large extent, traverse it, but some CGRP-immunoreactive influx appears to come from the intestine. The origin of intraganglionic substance P- and CGRP-immunoreactive fibres after ganglion transplantation remained unidentified. Somatostatin- and neuropeptide Y-immunoreactive fibres predominantly have an intraganglionic origin as have DBH-immunoreactive noradrenergic fibres. The demonstrated alterations in neuropeptide immunoreactivity of intraganglionic and periganglionic nerve fibres following the applied transsection procedures contribute to the present knowledge on origin and destination of peptidergic transmitter segments in the guinea pig inferior mesenteric ganglion. Moreover, the present study provides evidence that intrinsic participation in intraganglionic fibre supply is more extensive than hitherto believed.
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PMID:Immunohistochemistry of biogenic polypeptides in nerve cells and fibres of the guinea pig inferior mesenteric ganglion after perturbations. 336 35

The aim of the present review was to compare in mammals and amphibians the data concerning the presence of neuropeptides in the chromaffin cells and the possible action of these substances on adrenocortical cell function. Major homologies are to be found concerning the coexistence in chromaffin granules of catecholamines, Met-and Leu-enkephalins, and their precursor, proenkephalin A. However, the inhibitory action that might be exerted by enkephalins in vitro on corticosteroid production in mammalian adrenal gland, does not occur in amphibia. Dynorphin has been isolated in bovine adrenal medulla extracts; the presence of this opioid peptide has not been reported yet in amphibian interrenal tissue. All chromaffin cells of the frog interrenal gland contain VIP-like immunoreactivity whereas this neuropeptide is not contained in the adrenal medulla of mammals, exept in certain pheochromocytomas. In the frog, VIP, Metenkephalin and catecholamines are co-sequestered in the same chromaffin granules. In addition, synthetic porcine or chicken VIP stimulate in vitro the secretion of corticosteroids by frog interrenal fragments. In mammals, the steroidogenic action of VIP has been observed exclusively in tumor cell lines. The existence of somatostatin has been demonstrated in the human adrenal medulla and in pheochromocytomas, but not in amphibia. Somatostatin has been found to inhibit the response of adrenocortical cells to angiotensin II in mammals. A similar effect of somatostatin was not observed in amphibia. The coexistence of VIP and catecholamines in frog chromaffin granules and the stimulatory effect exerted by VIP on corticosteroidogenesis suggest that, in these animals, VIP may be co-liberated with noradrenaline during stress conditions, and thus may act locally on adrenocortical cells to stimulate corticosteroid secretion.
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PMID:[The coexistence of neuropeptides and catecholamines in the adrenal gland. Research on paracrine effects on adrenal cortex cells]. 608 55

A motor disorder similar to idiopathic Parkinson's Disease develops in rhesus monkeys after several daily repeated doses of N-methyl-4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP). The concentrations of peptides derived from proenkephalin A, proenkephalin B, substance P and somatostatin were measured by specific radioimmunoassays in the basal ganglia of MPTP-treated monkeys. In MPTP-treated monkeys, dynorphin B concentration was reduced in the caudate. In the putamen, the concentrations of peptides derived from both proenkephalin A and proenkephalin B were decreased. In the globus pallidus, the concentrations of all opioid peptides tend to be increased, reaching significance only for alpha-neo-endorphin. In the substantia nigra, only Met-enkephalin concentration was reduced, while other peptides derived from either proenkephalin A or proenkephalin B were not changed. Substance P and somatostatin were not changed in any brain area examined. Some of the symptoms associated with Parkinson's Disease may be related to altered activity of endogenous opiates in basal ganglia.
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PMID:Primate model of Parkinson's disease: alterations in multiple opioid systems in the basal ganglia. 615 Jul 50

1. The aim of this study was to investigate the neurochemical effects and measure the anatomical spread of infusion of c-fos antisense (AS) DNA into the striatum. 2. Rats were anesthetized and infused in opposing striata with c-fos AS and c-fos sense (S) DNA. Ten hours later they were injected with apomorphine (2 mg/kg, i.p.) and 20 min later they were overdosed with sodium pentobarbital and their brains either perfused or frozen. Vibratome-cut sections were immunostained for the detection of c-fos, JunB, Krox 24, somatostatin, substance P, dynorphin, tyrosine hydroxylase, and enkephalin. Cryostat-cut sections from the caudate were immunostained for the detection of c-fos, JunB, and Krox 24, as well as in situ hybridization for proenkephalin mRNA. Sections from the globus pallidus were used for the autoradiographic localization of D2 dopamine and A2a adenosine receptors. Sections from the substantia nigra were used for the autoradiographic localization of D1 dopamine and cannabinoid receptors. A second group of rats were injected in opposing striata with biotin-labeled c-fos AS DNA and c-fos S DNA. Ten hours later they were challenged with apomorphine (2 mg/kg, i.p.) and 20 min later brains were either perfused or frozen. Sections from these brains were cut throughout the rostral-caudal extent of the forebrain and the biotin labeled AS DNA was localized. 3. Krox 24 was expressed at high levels on the sense side of the brain in the striatum and overlying neocortex. However, on the AS-injected side there was a reduction in Krox 24 expression in striatum and overlying cortex. The biotin-labeled AS studies confirmed that the striatal infusion spread throughout the dorsal striatum as well as the overlying neocortex. We did not detect any changes in neurotransmitter receptors, neuropeptides, or tyrosine hydroxylase in AS/S-injected rat brains. 4. These results demonstrate that c-fos AS reduces Krox 24 expression in striatal and neocortical neurons but does not change the expression of a number of other proteins involved in basal ganglia function. Whether this effect is due to nonspecific actions of c-fos AS or to its effects on a component of the transduction pathway responsible for basal Krox 24 expression (NMDA receptors?) is unknown.
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PMID:c-fos antisense reduces expression of Krox 24 in rat caudate and neocortex. 762 2

One of the functions of glial receptors is to regulate synthesis and release of a variety of neuropeptides and growth factor peptides, which in turn act on neurons or other glia. Because of the potential importance of these interactions in injured brain, we have examined the role of two different receptors in the regulation of astrocyte neuropeptide synthesis. Stimulation of beta-adrenergic receptors on type 1 astrocytes resulted in increased mRNA and protein for the proenkephalin (PE) and somatostatin genes. This receptor also increased expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). The potential role of opiate receptors was examined in several ways. Treatment of newborn rats for 7 days with the opiate antagonist naltrexone, prior to preparation of astrocytes, had no effect on PE mRNA or met-enkephalin content but resulted in a significant increase in NGF content. However, treatment of astrocytes in culture with met-enkephalin, morphine, or naltrexone had no effect on any of these parameters. No opiate binding could be detected, using either etorphine or bremazocine, to membranes of astrocytes prepared from cortex, cerebellum, striatum, or hippocampus of 1-day, 7-day, or 14-day postnatal rats. Thus we conclude that type 1 astrocytes do not express opiate receptors and that the in vivo effects of naltrexone are mediated indirectly via some other cell type/receptor.
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PMID:Receptor-mediated regulation of neuropeptide gene expression in astrocytes. 792 46

Members of the C/EBP family of basic-leucine zipper (bZip) transcription factors form heterodimers and bind to the CAAT box and other sequence-related enhancer motifs. Using a 32P-labeled protein probe consisting of the bZip domain of C/EBP beta, we isolated a clone encoding C/EBP-related ATF (C/ATF), a bZip protein that heterodimerizes with C/EBP-like proteins but belongs to the CREB/ATF family. C/ATF homodimers do not bind to typical C/EBP DNA sites. Instead they bind to palindromic cAMP response elements such as that of the somatostatin gene. In addition, C/ATF-C/EBP beta heterodimers bind to a subclass of asymmetric cAMP response elements exemplified by those in the phosphoenolpyruvate carboxykinase and proenkephalin genes. Transient transfection studies indicate that interactions between C/ATF and C/EBP beta are the basis for a functional cross talk between these two families of transcription factors that may be important for the integration of hormonal and developmental stimuli that determine the expression of subsets of genes in specific cellular phenotypes.
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PMID:C/ATF, a member of the activating transcription factor family of DNA-binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs their binding to cAMP response elements. 850 17

This study was concerned with the distribution of a variety of putative neuromodulator and neurotransmitter systems in auditory regions of the rat brainstem using in situ hybridization histochemistry. Serial brain sections were screened for the presence of mRNAs for (i) precursors of the neuroactive substances cholecystokinin, somatostatin, proenkephalin and substance P (preprotachykinin), (ii) glutamic acid decarboxylase, the key synthesizing enzyme for GABA, or (iii) subunits alpha 1, alpha 2 and alpha 3 of the GABAA receptor. Detectable message for all of these probes was found in at least one auditory brainstem area. There were clear differences in the distribution of the various mRNAs in subregions of the inferior colliculus, superior olivary complex, lateral lemniscus and cochlear nucleus. Cells expressing mRNA for glutamic acid decarboxylase were most prominent in the inferior colliculus, but were also present in all lower auditory brainstem nuclei, except the medial superior olivary nucleus and medial nucleus of trapezoid body. The mRNA for GABAA alpha 1 receptor subunits was detectable in all auditory regions investigated, although at different levels of expression. GABAA alpha 2 and alpha 3 mRNA signals were seen in inferior colliculus, lateral lemniscus and in almost all superior olivary complex regions, but in fewer cells and at lower levels than the GABAA alpha 1 subtype. Moderate to high levels of preprocholecystokinin mRNA expression were seen in all subregions of the inferior colliculus. In other auditory brainstem areas, preprocholecystokinin mRNA levels were either low or absent. With regard to mRNAs for the neuroactive peptides somatostatin, preprotachykinin and preproenkephalin, all were expressed in the inferior colliculus but there were differences in their cellular distribution. For example, there were almost no preprotachykinin mRNA expressing cells in the central nucleus of inferior colliculus and levels of somatostatin mRNA were especially high in the dorsal cortex and in layer 3 of the external cortex of inferior colliculus. There were also differences in the pattern of expression of these mRNAs in the various brainstem auditory nuclei; there was no preprotachykinin mRNA in any part of the superior olivary complex, only somatostatin mRNA was found in the ventral cochlear nucleus, and expression of preproenkephalin mRNA was pronounced in the ventral nucleus of the trapezoid body and the rostral periolivary zone. The data are considered in light of the connectivity and functional organization of the auditory brainstem.
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PMID:Neurotransmitter and neuromodulator systems of the rat inferior colliculus and auditory brainstem studied by in situ hybridization. 871 77

Activation of both calcium and AMP-dependent regulatory pathways promotes survival of cerebellar neurons in vitro. Complex cellular programs such as survival must involve precise genetic responses. We show here, at the genomic level, that depolarization potentiates AMP-driven transcription of a variety of genes including the c-fos and c-jun proto-oncogenes, and the gene for somatostatin, proenkephalin and nerve growth factor. We used a reporter gene driven by the minimal AMP-responsive element (TGACGTCA) as a model system for studying this class of genes. In primary neurons, this reporter construct is co-activated in a synergistic manner by forskolin and KCl. We show that, in contrast to AMP, calcium-driven transcription does not require functional AMP-dependent protein kinase. Thus, when calcium and AMP levels are increased, these two second messengers stimulate transcription through different kinases which converge at the level of the AMP-responsive element. In addition, lower levels of intracellular free calcium can potentiate AMP-dependent transcription. This effect results from increased cyclic AMP accumulation and is strictly mediated by the AMP/AMP-dependent protein kinase pathway. In summary, low and high calcium concentrations potentiate AMP-dependent transcription via distinct mechanisms. Low calcium increases AMP production, whereas high calcium activates a non-cyclic AMP-dependent protein kinase, which in turn synergizes with AMP-activated transcription. These distinct mechanisms are likely to operate under specific physiological conditions within the neuronal network.
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PMID:Fine tuning of calcium entry into neurons regulates adenosine 3',5'-monophosphate-dependent transcription by several distinct mechanisms. 884 67

The gene coding for preprosomatostatin (ppSom), the molecular precursor of somatostatin (Som), is regulated at the level of transcription by calcium ions and cyclic-AMP [F. Baldino, S. Fitzpatrick-McElligott, T. O'Kane, I. Gozes, Hormonal regulation of somatostatin, Synapse 2 (1988) 317-325; M.R. Montminy, M.J. Low, L. Tapia-Arancibia, Cyclic AMP regulates somatostatin mRNA accumulation in primary diencephalic cultures and in transfected fibroblast cells, J. Neurosci. 6 (1986) 1171-1176.], or by agents which increase intracellular levels of cAMP directly, such as forskolin [M.R. Montminy, M.J. Low, L. Tapia-Arancibia, Cyclic AMP regulates somatostatin mRNA accumulation in primary diencephalic cultures and in transfected fibroblast cells, J. Neurosci. 6 (1986) 1171-1176.]. Transcriptional induction of the ppSom gene as examined in PC12 cells, transfected fibroblasts and primary diencephalic cultures, requires the highly conserved cAMP response element (CRE), which confers gene responsiveness to cAMP [M. Comb, N. Mermod, S.E. Hyman, Proteins bound at adjacent DNA elements act synergistically to regulate human proenkephalin cAMP inducible transcription, EMBO J. 7 (1988) 3793-3805; T. Tsukada, J.S. Fink, G. Mandel, Identification of a region in the human vasoactive intestinal polypeptide gene responsible for regulation by cyclic AMP, J. Biol. Chem. 262 (1987) 8743-8747.]. The ppSom gene is subject to stringent regulation during cerebrocortical development in vivo; however, little information is available regarding ppSom gene regulation by neurotransmitters or second-messengers in cortical neurons. We used primary cerebrocortical cell cultures from fetal mice to examine the dose-response and time-course of ppSom gene expression in response to the cyclic-AMP analogs, dibutyrl-cAMP (dbcAMP), and 8-bromo-cAMP (8-BrcAMP). We report a dose-response for both analogs in the range of 0.1-10 mM. Dose-response studies using agents which directly stimulate intracellular cAMP synthesis (forskolin) or inhibit its breakdown (3-isobutyl 1-methyl xanthine) were also performed. We observed an apparent synergistic effect on ppSom expression when used in combination. An increase in ppSom mRNA levels was observed by 4 h, with a maximal response at 12-24 h. No change in ppSom mRNA levels was observed in response to phorbol myristate acetate (PMA). Our findings confirm the specificity of ppSom gene regulation by cAMP and Ca2+ ions, and demonstrate the utility of using primary cerebrocortical cultures for the study of somatostatin gene expression by neurotransmitters and second-messengers as a model of human neurologic disorders.
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PMID:Regulation of the preprosomatostatin gene by cyclic-AMP in cerebrocortical neurons. 975 56

Double-label in situ hybridization was used to identify the phenotypes of striatal neurons that express mRNA for cannabinoid CB(1) receptors. Simultaneous detection of multiple mRNAs was performed by combining a (35)S-labeled ribonucleotide probe for CB(1) mRNA with digoxigenin-labeled riboprobes for striatal projection neurons (preprotachykinin A, prodynorphin, and preproenkephalin mRNAs) and interneurons (vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT), somatostatin, and glutamic acid decarboxylase (Mr 67,000; GAD67) mRNAs). To ascertain whether CB(1) mRNA was a marker for striatal efferents, digoxigenin-labeled probes for mRNA markers of both striatonigral (prodynorphin or preprotachykinin A mRNAs), and striatopallidal (proenkephalin mRNAs) projection neurons were combined with the (35)S-labeled probe for CB(1). A mediolateral gradient in CB(1) mRNA expression was observed at rostral and mid-striatal levels; in the same coronal sections the number of silver grains per cell ranged from below the threshold of detectability at the medial and ventral poles to saturation at the dorsolateral boundary bordered by the corpus callosum. At the caudal level examined, CB(1) mRNA was denser in the ventral sector relative to the dorsal sector. Virtually all neurons expressing mRNA markers for striatal projection neurons colocalized CB(1) mRNA. Combining a (35)S-labeled riboprobe for CB(1) with digoxigenin-labeled riboprobes for both preproenkephalin and prodynorphin confirmed localization of CB(1) mRNA to striatonigral and striatopallidal neurons expressing prodynorphin and preproenkephalin mRNAs, respectively. However, CB(1) mRNA-positive cells that failed to coexpress the other markers were also apparent. CB(1) mRNA was localized to putative GABAergic interneurons that express high levels of GAD67 mRNA. These interneurons enable functional interactions between the direct and indirect striatal output pathways. By contrast, aspiny interneurons that express preprosomatostatin mRNA and cholinergic interneurons that coexpress ChAT and VAChT mRNAs were CB(1) mRNA-negative. The present data provide direct evidence that cannabinoid receptors are synthesized in striatonigral neurons that contain dynorphin and substance P and striatopallidal neurons that contain enkephalin. By contrast, local circuit neurons in striatum that contain somatostatin or acetylcholine do not synthesize cannabinoid receptors. Published 2000 Wiley-Liss, Inc.
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PMID:Localization of cannabinoid CB(1) receptor mRNA in neuronal subpopulations of rat striatum: a double-label in situ hybridization study. 1084 53


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