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)

Although neuropeptides have been demonstrated to be hippocampal neuromodulators in laboratory animals, their role in human hippocampal physiology or pathophysiology remains to be defined. The concentrations of somatostatin, cholecystokinin octapeptide, vasoactive intestinal polypeptide, and dynorphin A 1-17 were determined in hippocampal tissue resected from patients with cryptogenic temporal lobe epilepsy, a common seizure disorder originating in or near the hippocampus. Control tissue was obtained from cadavera or epilepsy patients in whom the hippocampus was removed during the resection of temporal lobe tumors. Peptide determinations were performed on extracts of punch biopsy specimens taken from six different hippocampal regions. A significant decrease in immunoreactive somatostatin concentration was identified in the dentate gyrus and in region cornu ammonis 4 of cryptogenic temporal lobe epilepsy specimens. No significant changes were present in any other hippocampal region or in the levels of other peptides. In situ hybridization studies performed on cryostat sections from similar patients confirmed a marked loss of neurons expressing the somatostatin gene, which was restricted to the dentate hilus. The density of specific 125I-somatostatin binding to cryostat sections, as determined by semiquantitative in vitro autoradiography, was significantly increased in the dentate gyrus of the cryptogenic epilepsy patients, compared with tumor control specimens. We conclude that a loss of somatostatin-producing interneurons with an upregulation of dentate somatostatin receptors is a specific and characteristic element in the pathophysiology of human cryptogenic temporal lobe epilepsy.
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PMID:A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy. 167 46

Three human breast cancer cell lines ZR-75-1, MDA-MB-436 and MCF-7 were found to contain respectively, 3.06, 2.69 and 1.86 fmol of somatostatin-like immunoreactivity (SLI) per 10(6) cells. Since SLI is undetectable in the passaging media it must, therefore, be synthesised by the cells. In the presence of fetal calf serum the cells were growth inhibited by addition of somatostatin or its long-lasting analogue, Sandostatin, but only after 3 days of continuous exposure. A 1-day exposure to either peptide had little or no effect on subsequent cell growth in peptide-free medium. Inhibition of cell proliferation is not due to cytotoxic effects of the dose used (500 ng ml-1, each) since both peptides caused short-term stimulation of growth in the absence of serum.
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PMID:Synthesis of somatostatin by breast cancer cells and their inhibition by exogenous somatostatin and sandostatin. 256 8

Epinephrine's effect to increase metabolic rate is accompanied by changes in the plasma concentrations of insulin, glucagon, and metabolic substrates. Because both glucagon and insulin have been reported to affect thermogenesis, these hormones might contribute to or modify the thermogenic response to epinephrine. To determine if the epinephrine-induced increase in metabolic rate is secondary to changes in glucagon or insulin or to changes in the fuels modulated by these hormones, metabolic rate was measured by indirect calorimetry in five normal weight post-absorptive young men on three occasions: study A, an intravenous epinephrine infusion alone; study B, a 4-h "islet clamp" consisting of somatostatin infusion with basal insulin and glucagon replacement; and study C, an intravenous epinephrine infusion combined with the islet clamp. A 1-h base-line period preceded 2 h of epinephrine infusion. During the 4-h islet clamp (study B), metabolic rate and plasma concentrations of epinephrine, insulin, glucagon, and glucose remained unchanged. During the infusion of epinephrine alone (study A), metabolic rate and concentrations of glucagon, free fatty acids, and C-peptide increased as expected. Also as expected, the glycemic response to epinephrine infusion was much larger when insulin and glucagon levels were fixed with the islet clamp (study C). In contrast, the metabolic rate and the free fatty acid concentration responded similarly to epinephrine infusion when insulin and glucagon were fixed (study C) and when they were changing (study A). We conclude that epinephrine increases metabolic rate independently of physiological changes in plasma glucagon or insulin or the circulating fuels they modulate.
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PMID:Epinephrine's effect on metabolic rate is independent of changes in plasma insulin or glucagon. 256 29

While several peptides have been shown to coexist in perikarya within dorsal root ganglia of rat, coexistence of peptides has not been confirmed in axons associated with these neurons. In this study, the coexistence of substance P (SP) with somatostatin (SOM), calcitonin gene-related peptide (CGRP), dynorphin A 1-8 (DYN), neurotensin (NT), galanin (GAL), and 5-HT in varicosities was visualized using fluorescence immunohistochemistry. Densities of immunoreactive varicosities within laminae I and II of the dorsal horn of the rat spinal cord were quantified by computer-assisted image analysis. Decreases in densities of immunoreactive varicosities as a result of multiple unilateral dorsal rhizotomies were used to determine proportions of immunoreactive varicosities associated with primary afferent neurons. Three observations were made. (1) Dorsal rhizotomy depleted greater than one-third of the varicosities individually immunoreactive for SP, SOM, GAL, or DYN, confirming the association of these peptides with primary afferent neurons. (2) SP coexisted with CGRP, GAL, and DYN in varicosities within the dorsal horn of normal animals. (3) CGRP-, SP+CGRP-, and SP+GAL-immunoreactive varicosities were nearly depleted following dorsal rhizotomy. The depletion of these peptides, particularly in combination, indicates that they may be used as markers for varicosities of some primary afferent neurons within the superficial laminae of the dorsal horn of the rat spinal cord.
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PMID:A quantitative study of the coexistence of peptides in varicosities within the superficial laminae of the dorsal horn of the rat spinal cord. 264 83

A 1-l soap enema given to nine healthy volunteers elicited significantly elevated plasma levels of vasoactive intestinal polypeptide (VIP) and cholecystokinin (CCK), together with a transient somatostatin peak. These rises coincided with significant rises both in systolic and diastolic blood pressure, whereas plasma levels of motilin and pancreatic polypeptide remained unchanged. It is suggested that the peptide releases are of colonic origin and that VIP and CCK may play mediatory roles in the enema-induced defecation.
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PMID:Release of gastrointestinal regulatory peptides after a soap enema. 286 69

A 1 1/2 year old child developed profuse watery diarrhoea, shown to be due to excessive plasma vasoactive intestinal peptide (VIP) levels, whilst on treatment for metastatic neuroblastoma. Because it was unresponsive to alternative treatment, an attempt was made to control the diarrhoea with a somatostatin infusion. The attempt failed despite the fact that serum VIP levels were substantially reduced. Possible reasons for failure are discussed and the importance of plasma VIP as a marker for maturation in neuroblastoma emphasised.
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PMID:Intractable diarrhoea in a patient with vasoactive intestinal peptide-secreting neuroblastoma. Attempted control by somatostatin. 611 74

The role of cytoskeletal microtubules and microfilaments in modulating cAMP generation in S49 lymphoma cells was investigated using the agents colchicine and cytochalasin B, respectively, which are known to disrupt these structures. A 1-hr pretreatment of S49 cells with 10 microM colchicine typically enhanced maximal isoproterenol-(beta-adrenergic receptor) stimulated cAMP accumulation by 100%, whereas cytochalasin B increased isoproterenol-stimulated cAMP by 30%. The combination of colchicine and cytochalasin B synergistically enhanced agonist-stimulated cAMP to 225% over control values. A synergistic increase in cAMP accumulation was also observed in cells treated with the agonist prostaglandin E1 or cholera toxin (which activates the stimulatory guanine nucleotide regulatory (Gs) protein). Colchicine and cytochalasin B did not ablate the inhibitory effects of somatostatin or the stimulatory effect of pertussis toxin treatment on beta-receptor-stimulated cAMP accumulation, indicating that these cytoskeletal disrupting agents do not enhance responsiveness in S49 cells via alterations in the inhibitory guanine nucleotide regulatory protein pathway. Moreover, colchicine, but not cytochalasin B treatment, enhances expression of isoproterenol-promoted 3H-forskolin binding in intact cells (a measure of Gs/adenylyl cyclase coupling). Thus, colchicine and cytochalasin B appear to enhance signaling in the Gs/adenylyl cyclase pathway by alterations of components distal to hormone receptors, most likely at the Gs protein and/or via cAMP generation. These results imply that microtubules and microfilaments can interact in the regulation of this pathway and that increases in cellular cAMP may contribute to the action of drugs that alter function of these cytoskeletal elements.
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PMID:Colchicine and cytochalasin B enhance cyclic AMP accumulation via postreceptor actions. 763 57

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.
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PMID:Effect of somatostatin on circadian rhythms of firing and 2-deoxyglucose uptake in rat suprachiasmatic slices. 790 18

The effect of the dopamine agonist bromocriptine and the somatostatin analog SMS 201-995 on growth of 12 human somatotrophic and 13 non-functioning adenoma cell cultures was investigated. When adenoma cells were maintained in medium supplemented with 5% fetal calf serum, cell counts of 10 of 12 somatotrophic cultures increased to 145 +/- 6 and 171 +/- 9% (mean +/- SD) and in 12 of 13 non-functioning cell cultures up to 125 +/- 12 and 217 +/- 15% after 3 days of incubation. In most cases bromocriptine and SMS 201-995 dose dependently (1 nmol/l to 10 mumol/l) inhibited adenoma cell growth but there was only (1, 10 mumol/l) a significant inhibitory effect at high doses of both drugs. A 1 mumol/l concentration of bromocriptine decreased cell counts of 5 of 12 somatotrophic cell cultures (range 84 +/- 3 to 76 +/- 6% vs control = 100%) and in 5 of 13 non-functioning cell cultures (range 85 +/- 4 to 71 +/- 7%). A 10 mumol/l concentration of bromocriptine decreased cell counts in all 12 somatotrophic (range 87 +/- 1 to 61 +/- 8%) and in 12 of 13 non-functioning adenoma cultures (range 87 +/- 6 to 57 +/- 3%). Bromocriptine specifically inhibited growth because its effect could be reversed by the dopamine D2-receptor antagonist haloperidol. Both 1 and 10 mumol/l SMS 201-995 significantly decreased cell counts in three of six somatotrophic (87 +/- 3 to 38 +/- 3%) cell cultures. In two of five cases growth of non-functioning adenoma cultures was suppressed by 1 mumol/l SMS 201-995, and in four of five cases by 10 mumol/l (86 +/- 3 to 74 +/- 4%). The growth inhibitory effect of both bromocriptine and SMS 201-995 was not just due to an effect on growth of fibroblasts contaminating the adenoma cell cultures, because it could be observed also when adenoma cells were maintained in a D-valine-supplemented medium that suppresses fibroblast growth. In summary, both bromocriptine and SMS 201-995 at high doses were able to inhibit cell growth of cultured somatotrophic and non-functioning adenomas in vitro. However, the mechanism of this inhibitory effect is not yet well understood.
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PMID:Effect of bromocriptine and SMS 201-995 on growth of human somatotrophic and non-functioning pituitary adenoma cells in vitro. 812 83

A metalloendopeptidase (MEP) isolated from rabbit liver microsomes with substrate specificity for peptides containing Arg at the P1 and P4 positions has recently proved to be identical to soluble angiotensin-binding protein present in the cytosol. Here we describe the peptide-degrading specificity of MEP, determined using various bioactive peptides and novel fluorogenic substrates for the enzyme. MEP degraded oligopeptides, including bradykinin, alpha-neoendorphin, bovine adrenal medulla dodecapeptide, substance P, bombesin, neurotensin, and alpha-endorphin, but not polypeptides such as reduced lysozyme and histone H4, hence, MEP probably belongs to the family of endo-oligopeptidases. It cleaved most preferentially at the -Phe-Ser- bond of bradykinin (kcat/Km = 2.8 x 10(4) M-1.S-1) but did not cleave high molecular weight and low molecular weight kininogens, the precursors of bradykinin. MEP did not cleave angiotensin I, dynorphin A 1-13, somatostatin, and luteinizing hormone-releasing hormone, some of which are good substrates for metalloendopeptidase-24.15, metalloendopeptidase-24.16, N-arginine dibasic convertase, and yeast endopeptidase-24.15 related peptidase. An active site-directed inhibitor of metalloendopeptidase-24.15, N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate also had no effects on the amidolytic activity of MEP. Based on the cleavage sites of bioactive peptides and processing sites of vitamin K-dependent proproteins, intramolecularly quenched fluorogenic peptide substrates were newly synthesized. Among the thirteen substrates used, the most reactive was 2-aminobenzoyl-Ala-Arg-Val-Arg-Arg-Ala- Asn-Ser-2,4-dinitroanilinoethylamide (kcat/Km = 9.3 x 10(5) M-1.S-1). An angiotensin antagonist, [Sar1, Ala8]-angiotensin II, inhibited hydrolysis of the substrate by MEP in a competitive manner (Kl = 7.6 microM). MEP cleaved oligopeptides even on the carboxyl side of proline residue and these peptides are resistant to hydrolysis by the cytosol-derived proteasome, therefore MEP may participate in the catabolism of oligopeptides in the cytosol, together with other endo-oligopeptidases.
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PMID:Substrate specificity of rabbit liver metalloendopeptidase and its new fluorogenic peptide substrates. 857 4


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