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)

In order to establish an in vitro model of Huntington's disease, we prepared slice cultures of striatal tissue from newborn rats. The striatal cultures were grown for 12-39 days in the absence of any other brain tissue. The presence of specific cell markers was shown by immunocytochemistry, histochemistry and in situ hybridization with alkaline-phosphatase-labeled oligonucleotide probes. We focused on (1) the medium-sized, aspiny interneurons, which in vivo express the neuropeptides somatostatin and neuropeptide Y and the nitric oxide synthesizing enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, and which are spared in Huntington's disease and (2) the enkephalinergic, medium-sized projection neurons, which are particularly vulnerable in Huntington's disease. Similar basic morphologies of the presumed interneurons and double staining of NADPH-diaphorase positive and somatostatin immunoreactive neurons suggest that the two neuropeptides and NADPH-diaphorase are extensively colocalized in the cultures, as in vivo. In the newborn rats, included as controls, a patch-matrix distribution of the NADPH-diaphorase staining is described for the first time. In the striatal slices the distribution of the NADPH-diaphorase staining stayed uneven after 3-5 weeks in culture, with areas almost devoid of staining alternating with more heavily stained areas. This pattern may represent an intermediate stage between the patch-matrix distribution in the newborn and the homogeneous staining in the adult rat striatum. From quantitative estimates we found the same mutual rank order of the numbers of neuropeptide Y- and somatostatin-immunoreactive neurons and NADPH-diaphorase positive neurons in vivo and in vitro. Both in the slice cultures and in the brain, the number of enkephalin mRNA-containing neurons significantly exceeded that of neuropeptide Y- and somatostatin mRNA-containing neurons. This implies that the mutual distribution of presumed interneurons and projection neurons was preserved in the slice cultures. Comparison of cell numbers per unit volume showed that, in the cultures, the number of presumed interneurons, with the exception of NPY mRNA-containing neurons, significantly exceeded that in vivo. In contrast, the enkephalin mRNA-containing neurons, which in vivo are projection neurons, were significantly fewer in the cultures. The relative loss of projection neurons and preservation of interneurons in single slice cultures of striatal tissue apparently mimick some of the neurodegenerative changes of Huntington's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Organotypic slice cultures of the rat striatum: an immunocytochemical, histochemical and in situ hybridization study of somatostatin, neuropeptide Y, nicotinamide adenine dinucleotide phosphate-diaphorase, and enkephalin. 761 39

Recent studies have demonstrated the biological importance of the interaction of nitric oxide (NO) with proteins. Protein-associated targets of NO include heme, Cys, and Tyr. Electrospray ionization-mass spectrometry was used to monitor the results of exposure of model peptides and an enzyme to NO under different conditions and thus addressed aspects of NO-protein interactions. The molecular mass of a decapeptide containing a single Cys residue increased by 29 Da upon treatment with NO under aerobic and acidic conditions, consistent with the substitution of one NO moiety. The mass of reduced somatostatin, a peptide containing two Cys residues, increased by 58 Da, consistent with the substitution of two NO moieties. These substitutions were prevented by pretreatment of the peptides with N-ethylmaleimide. The strength of the nitrosothiol bond was examined by varying the amount of energy applied to the peptide ions and indicated a labile species. Cys residues were very rapidly nitrosated, while other reactions were observed to occur at much slower rates. These include the further oxidation of nitrosothiol to sulfonic acid and nitration of Tyr. Peptides treated with NO at physiological pH were observed to undergo dimerization as well as nitrosation. These studies were extended to the enzyme p21ras, whose activity has been postulated to be modulated by nitrosothiol formation, and revealed the formation of a single nitrosothiol on p21ras upon NO treatment. These data suggest that electrospray ionization-mass spectrometry allows for quantitation and characterization of nitrosothiol bonds in peptides and proteins.
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PMID:Monitoring reactions of nitric oxide with peptides and proteins by electrospray ionization-mass spectrometry. 761 15

The present experiments were devoted to analyzing the hypothesis that somatostatin (SS) could modulate glomerular filtration rate by interacting with mesangial cells. Studies were performed in cultured human mesangial cells, passages 3-5. Radioligand experiments demonstrated the presence in the cells of two kinds of receptors, with high (dissociation constant 14 pM. Number of sites: 426 fmol/mg) and low (dissociation constant 56 pM. Number of sites: 20, 111 fmol/mg) affinity. SS prevented in a dose-dependent manner the reduction in planar cell surface area induced by 100 nM Angiotensin II (AII). This effect was not inhibited by the blockade of the vasorelaxing prostaglandins (indomethacin, 10 microM), nitric oxide (L-N-methyl-arginine, 0.2 mM), adenylate cyclase (2,5'-dideoxyadenosine, 0.1 mM), or guanylate cyclase (Methylene blue, 30 microM; LY-83583, 10 microM), but it was potentiated by zaprinast, an inhibitor of the cyclic GMP (cGMP)-specific phosphodiesterase. SS also blocked the increase in myosin light chain phosphorylation induced by AII. SS increased cGMP synthesis by cultured human mesangial cells, an effect that seemed to be dependent on the stimulation of a particulate guanylate cyclase. Preincubation of the cells with pertussis toxin (0.5 microgram/ml) inhibited the effect of SS on the AII-dependent changes in planar cell surface area, as well as the SS-dependent cGMP stimulation. In summary, these results demonstrate the ability of SS to relax cultured human mesangial cells, thus supporting a role for this peptide in the regulation of the glomerular filtration rate. The SS-dependent mesangial cell relaxation may be due to changes in the intracellular concentrations of cGMP, as a consequence of the activation of a particulate guanylate cyclase.
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PMID:Effects of somatostatin on cultured human mesangial cells. 762 80

Isolated perfused segments of canine ileum have no spontaneous motor activity and release large quantities of vasoactive intestinal polypeptide (VIP) continuously. Somatostatin perfusion was shown to decrease VIP release, accompanied by increased contractions and amplification of responses to low-frequency electrical field stimulation. After perfusion of higher somatostatin concentrations, the VIP output did not recover but quiescence returned. The actions of somatostatin on motor activity were not modified by hexamethonium, slightly reduced by atropine, and markedly reduced by tetrodotoxin. Inhibition of VIP output was not the major determinant of motor activity in the ileum because 1) a second infusion of somatostatin had similar motor effects despite markedly reduced VIP output, 2) abolition of tonic VIP output did not prevent induction of motor activity by somatostatin, and 3) artificial restoration of VIP levels did not prevent or antagonize somatostatin-induced ileal contractions. In contrast, the increment in motor responses induced by somatostatin was not apparent after N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase, but recovered after reversal by L-arginine. We conclude that the mode of somatostatin activation of intestinal motor activity involves reduced NO output, enhanced excitatory mediator action or release, a direct action on smooth muscle, and possibly inhibition of VIP output. Of these, reduced NO output plays the most important role.
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PMID:Somatostatin excites canine ileum ex vivo: role for nitric oxide? 763 89

The aim of this study was to investigate the mechanism of action of somatostatin on the circular muscle of the isolated canine ileum using the microelectrode technique. The membrane potential from circular muscle cells was recorded in two preparations: 1) whole thickness circular and longitudinal muscle (with intact myenteric and deep muscular plexuses, n = 13) and 2) isolated circular muscle (with only deep muscular plexus, n = 9). In this preparation, inhibitory junction potentials (IJPs), elicited after field stimulation, are mediated by a nitric oxide-related (NO-R) compound. Somatostatin (10(-6) M) transiently (2-5 min) depolarized the circular muscle cells in both whole thickness (3.6 +/- 1.0 mV, P < 0.01) and isolated circular muscle preparations (8.0 +/- 0.8 mV, P < 0.01). Somatostatin did not reduce either the amplitude or duration of the IJP in the isolated circular muscle but reduced slow-wave amplitude. In contrast, a reduction (20-50%) in the amplitude of the IJP was observed in the whole thickness preparation, and there was little effect on slow-wave amplitude. Somatostatin did not affect the induced slow wave observed in the whole thickness preparation after field stimulation. Apamin significantly reduced the amplitude of the IJP in both preparations. Somatostatin (10(-6) M) did not modify the apamin-resistant IJP. A reduction in the slow-wave amplitude was observed in the isolated circular muscle preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of action of somatostatin on the canine ileal circular muscle. 763 97

We analyzed the distribution and light-microscopic features of the NADPH diaphorase-containing structures in the lizard hippocampus, likely to correspond to nitric oxide synthase-containing cells and fibers, and thus likely to release nitric oxide. We also studied co-localization of NADPH diaphorase with the neurotransmitter GABA, the calcium-binding protein parvalbumin, and the neuropeptide somatostatin, in order to examine whether putative nitric oxide-synthesizing neurons represent a different subpopulation of GABA cells, on which the authors recently reported in lizards. We also studied co-localization of NADPH diaphorase with parvalbumin or somatostatin in mice to ascertain whether the characteristics of this population in reptiles parallel the situation in mammals. Most of the positive NADPH diaphorase neurons were stained in a Golgi-like manner and were in the plexiform layers of the lizard hippocampus with morphologies ranging from bipolar to multipolar. Co-localization with GABA was 100%, and NADPH diaphorase-positive neurons in the lizard hippocampus did not contain parvalbumin or somatostatin. The results indicate that putative nitric oxide-synthesizing neurons represent a distinct subpopulation of GABA interneurons in the lizard hippocampus. Two different types of fibers were described in the plexiform layers: one type bearing thick varicosities, and the other thinner ones. We discuss the possibility that at least part of the positive fibers arise from a hypothalamic aminergic nucleus contacting the third ventricle, the periventricular hypothalamic organ. Most radial glia were stained almost completely and formed typical end-feet both at the pia and around capillaries. The results of this study confirm that the capacity for synthesizing nitric oxide is linked to a determined set of neuronal markers depending on the specific brain region, and they provide new resemblances between hippocampal regions in different classes of vertebrates.
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PMID:NADPH diaphorase-positive neurons in the lizard hippocampus: a distinct subpopulation of GABAergic interneurons. 778 47

Previous work has shown that growth hormone-releasing factor (GRF) stimulates cGMP production and somatostatin [somatotropin (growth hormone)-release-inhibiting factor, SRIF] release without altering cAMP accumulation by fragments of median eminence incubated in vitro. Therefore, this study was undertaken to evaluate the effect of GRF and cGMP on SRIF mRNA and SRIF release in the periventricular nuclei of male rats in vitro. SRIF mRNA levels were determined in explants of periventricular nuclei incubated for 6 hr in Waymouth's medium in the presence of various substances. Steady-state levels of SRIF mRNA were measured by an S1 nuclease protection assay using a 32P-labeled rat SRIF RNA probe. SRIF release and cGMP formation were measured at 30 min and 6 hr by RIA. SRIF mRNA levels and SRIF release were significantly (P < 0.025) increased (approximately 2-fold) by 1 microM dibutyryl cGMP, whereas sodium butyrate had no effect. This augmentation was not influenced by cycloheximide, an inhibitor of protein synthesis. Sodium nitroprusside (10 microM), an activator of the guanylate cyclase pathway via its release of nitric oxide, augmented (P < 0.001) SRIF mRNA levels and significantly increased (P < 0.05) SRIF release. GRF (1 nM) increased SRIF mRNA (P < 0.001) and stimulated the release of SRIF at 30 min (P < 0.05) and 6 hr (P < 0.01). This stimulation was abolished by 10 microM NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase, but not by NG-monomethyl-D-arginine (D-NMMA, the inactive isomer). GRF also increased cGMP formation. This effect was completely blocked by incubation with L-NMMA but not D-NMMA. These results indicate that GRF releases nitric oxide. The nitric oxide diffuses to the adjacent SRIF neurons, where it activates guanylate cyclase, leading to increased formation of cGMP. This cGMP increases SRIF mRNA and SRIF release in the periventricular nuclei of male rats.
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PMID:Growth hormone-releasing factor increases somatostatin release and mRNA levels in the rat periventricular nucleus via nitric oxide by activation of guanylate cyclase. 790 58

This review summarizes the recent findings on the localization of somatostatin (SRIF)-related peptides in local circuit interneurons and long projection neurons. These differential locations are discussed in relation to the multiple roles of SRIF 14 and SRIF 28 in neuroendocrine and autonomic regulation. The coexistence of SRIF with other neuropeptides and neurotransmitters, including nitric oxide, is described. The pharmacological and functional properties of the recently cloned family of SRIF receptor subtypes are reviewed as well as their localization. Finally, the decrease in SRIF concentrations in the cerebrospinal fluid (CSF) and the central nervous system (CNS) commonly associated with Alzheimer's disease is critically evaluated.
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PMID:The neurobiology of somatostatin. 790 81

The motility of the gallbladder (GB) consists of collection, storage and delivery of bile. GB motor functions are controlled by its extrinsic and intrinsic innervation, and humoral factor. In the fasting stage, GB motility is associated with phase 3 of the interdigestive migrating myoelectric complex and increased plasma motilin concentrations. In the fed state cholecystokinin (CCK) is the primary mediator of GB contraction. Extrinsic neural control of GB motility appears to play a role in the mediation of cephalic phase of GB emptying. Vagal stimulation induces GB concentration, and sympathetic stimulation induces GB relaxation via cholinergic, adrenergic, and noncholinergic, nonadrenergic neurotransmitters. Intrinsic neural control of GB motility is mediated by such neuropeptides as pancreatic polypeptide, somatostatin, bombesin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal polypeptide, CCk, tachykinins and nitric oxide.
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PMID:[Neurohormonal regulation of gallbladder motility]. 791 87

The interplay of somatostatin, gamma-aminobutyric acid (GABA), and opioid neurons in the regulation of the descending relaxation phase of peristalsis was examined in isolated rat colonic segments. Release of somatostatin, GABA, vasoactive intestinal peptide (VIP), and L-[3H]citrulline [coproduct and index of nitric oxide (NO) production] increased, and release of Met-enkephalin decreased, during descending relaxation. Somatostatin antiserum (1:50) inhibited GABA and L-[3H]citrulline and reversed Met-enkephalin from decrease below to increase above basal level; exogenous somatostatin had the opposite effect. Bicuculline (GABAA antagonist) inhibited L-[3H]citrulline, had no effect on somatostatin, and reversed Met-enkephalin from decrease below to increase above basal level; exogenous GABA had the opposite effect. Naloxone increased GABA and L-[3H]citrulline but had no effect on somatostatin; exogenous Met-enkephalin had the opposite effect. In all instances the changes in L-[3H]citrulline paralleled those previously obtained with VIP. The results are consistent with the operation of a circuit in which somatostatin neurons inhibit the activity of opioid neurons, causing a decrease in Met-enkephalin. The decrease in Met-enkephalin initiated by somatostatin is accentuated by a reciprocal inhibitory pathway linking GABA and opioid neurons. The decrease in Met-enkephalin eliminates the inhibitory influence of opioid neurons on VIP/NO neurons and leads to increase in VIP, NO, and descending relaxation.
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PMID:Interplay of somatostatin, opioid, and GABA neurons in the regulation of the peristaltic reflex. 794 34


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