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)

We studied the functional coupling between antral somatostatin and gastrin cells in pigs using isolated perfused preparations of the antrum with intact supply of the vagus nerves. Luminal acidification significantly inhibited gastrin secretion to 61 +/- 3% of basal secretion and increased somatostatin output 9-fold. Intra-arterial infusion of somatostatin to concentrations of 10(-10) and 10(-9) mol/l inhibited gastrin secretion to 18 +/- 9 and 33 +/- 11% of basal secretion. Electrical stimulation of the vagus nerves and intra-arterial infusion of gastrin-releasing polypeptide (GRP; 10(-9) mol/l) significantly increased both gastrin and somatostatin secretion. Addition to the perfusate of Fab fragments of somatostatin antibodies abolished the effect of somatostatin at 10(-10) mol/l and the acid inhibition of gastrin secretion, but had no effect on the response to vagus stimulation of GRP infusion. We conclude that a local release of somatostatin is essential for the acid-induced inhibition of gastrin secretion, whereas changes in the local somatostatin concentration are unlikely to play a major role in vagally or GRP-induced gastrin secretion.
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PMID:Somatostatin is an essential paracrine link in acid inhibition of gastrin secretion. 135 90

In vitro degradation of 125I-labeled somatostatin-14 (Tyr11) [I-SS-14(Tyr11)] by luminal flushings of rat gastrointestinal segments was studied to characterize the fate of somatostatin in the gastrointestinal lumen. In addition, we evaluated the effect of rat milk as a potential inhibitor of luminal degradation of 125I-SS-14(Tyr11). Degradation of 125I-SS-14(Tyr11) was not detected in stomach flushings from either suckling or weanling rats. Luminal flushings from the small intestine degraded 125I-SS-14(Tyr11), with a gradient increase of activity from duodenum to midjejunum (degradation in suckling rat midjejunum and ileum was about five times lower than that in weanling rat). Degradation of 125I-SS-14(Tyr11) by luminal flushings of suckling rat midjejunum was dose dependently inhibited by rat milk casein and soluble fractions. Inhibitory activity of rat milk soluble fraction was heat labile and several times more potent than that of casein fraction. Casein fraction appeared to be stable at 100 degrees C for up to 30 min of exposure. These studies suggest that somatostatin is stable in the gastric lumen and that milk protects somatostatin from intestinal luminal proteolysis, indicating a possible physiological significance of milk-borne SS-14 for the suckling rat gastrointestinal tract.
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PMID:Inhibition of intestinal degradation of somatostatin by rat milk. 196 33

In the present study we investigated the effect of antiepileptic drugs on high potassium (50 mM) stimulated somatostatin release in rat cortical slices in a superfusion system. The somatostatin-like immunoreactivity (SLI) in superfusate was determined by radioimmunoassay. The antiepileptic drugs studied, vigabatrin, valproate, carbamazepine, phenobarbital, primidone, clonazepam and phenytoin were tested at a concentration range of 1-1000 microM). Of the drugs used vigabatrin had the most significant inhibitory effect on SLI release (IC50 = 240 microM). Vigabatrin also caused a concomitant, dose-dependent increase in superfusate gamma-amino butyric acid (GABA) level. A 30% decrease in the release of SLI followed incubation with valproate and carbamazepine, but only at high drug concentrations (1000 microM). Phenobarbital, primidone, clonazepam and phenytoin did not affect SLI release. Addition of GABA to superfusate caused a dose-dependent decrease in the amount of SLI release (IC50 = 56 microM). In conclusion, at low concentrations the antiepileptic drugs had only minor effects on SLI release. At higher concentrations, however, vigabatrin and valproate decreased the release of SLI, which may relate to their ability to elevate tissue levels of GABA.
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PMID:Effect of antiepileptic drugs on somatostatin release in vitro. 198 Mar 51

Somatostatin is released in the blood, in synaptic clefts, and in the intercellular space in response to a variety of stimuli. In view of its multiple functions, various sites of synthesis and release, and rapid inactivation, as well as extremely low levels of somatostatin in the peripheral blood, somatostatin can hardly be considered to be a hormone whose target is reached via the general circulation. The target organs of cells may be located near the somatostatin-producing cells and can be reached via local circulation such as the hypophyseal portal system and the microportal circulation in the gut mucous membrane. Somatostatin released from the neurons acts as a hypophyseotropic hormone and a neurotransmitter or neuromodulator. Furthermore, somatostatin may also act in a paracrine fashion by being released into the intercellular space. This space may sometimes be compartmentalized by tight junctions so that the action of the peptide is limited only to the adjacent cells. In this fashion, the pancreatic islet somatostatin influences nearby A- and B- cell activities. Gut D cells, prototypes of APUD or paraneuron cells, show considerable similarity to neurosecretory cells not only in biochemical processes but also morphologically. While the somatostatin neurons in the brain respond to dopaminergic and catecholaminergic agonists, D cells in the gut respond to chemical stimuli in the lumen by sensing them with microvilli. They release somatostatin into the blood stream, into the intercellular space, and into the gastric and intestinal lumen. Luminal somatostatin may affect other endocrine and nonendocrine cells in the mucous membrane of the gut. It is noted that the same stimulatory agent does not always stimulate somatostatin release from different organs; one agent stimulates the release from one organ and suppresses release from the other organ.
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PMID:Somatostatin: regulation of secretion. 611 25

Phorbol diester tumor promoters are potent cocarcinogens which also possess activity in a variety of biological assays. We have examined the effect of phorbol diesters on secretion of somatostatin-like immunoactivity (SRIF-LI) by dispersed cells of fetal rat brain maintained in long term culture. Phorbol-12-myristate-13-acetate (PMA) and phorbol 12, 13-dibutyrate stimulate SRIF-LI secretion in a dose-dependent fashion. 4-O-Methyl-PMA is approximately 100 times less potent than phorbol 12, 13-dibutyrate. 4-beta-Phorbol was inactive. Treatment with a nonphorbol irritant, teleocidin, also was associated with significantly augmented release of SRIF-LI. Significant stimulation is seen within 7.5 min of treatment and response is linear over 1 h. Administration of phorbol diesters in low calcium buffer (0.1 mM) with or without cobalt or pretreatment with verapamil are associated with significantly diminished secretion. Substitution for sodium ion by choline or pretreatment with tetrodotoxin (10(-7) M) also inhibits response to PMA. gamma-Aminobutyric acid (50 microM) or the gamma-aminobutyric acid agonist muscimol (5 microM) decrease response to PMA as does sodium pentobarbital (IC50 approximately 30 microM). Phenobarbital is less potent as an inhibitor; significant suppression is not seen until approximately 300 microM. The data are consistent with an action for phorbol diesters mediated at least in part by voltage dependent sodium channels and calcium influx into excitable cells. Inhibition by hyperpolarizing agents is compatible with this mechanism. Phorbol diesters may thus mimic endogenous modulator substances active at the nerve cell membrane.
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PMID:Phorbol diesters stimulate somatostatin secretion from cultured brain cells. 640 21

Luminal application of acid was recently shown to stimulate surface epithelial HCO3(-) transport in stomach and duodenum. Effects of some potential transmitters of this response were therefore studied in amphibian gastric fundic and proximal duodenal mucosa in vitro. Duodenal HCO3- transport, which could be titrated directly, was stimulated by dibutyryl cAMP (DBcAMP, 10(-6) M), the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-6) M), noradrenaline (10(-6) M), pancreatic glucagon (10(-8) M), and gastric inhibitory peptide (GIP, 10(-10) M). Stimulation by glucagon, but not by prostaglandin E2 (PGE2, 10(-6) M), required Cl- in the luminal solution and was prevented by furosemide (10(-3) M). This suggests that glucagon may affect HCO3(-)-Cl- exchange at the luminal membrane while transport stimulated by prostaglandins may be electrogenic. Stimulatory effects of glucagon and PGE2 were also additive. Gastric HCO3- transport, studied in tissues after inhibition of H+ secretion by histamine H2-antagonists, clearly differed from duodenum in that noradrenaline and GIP were inhibitory and DBcAMP was without effect. Stimulation of gastric HCO3- transport was observed with glucagon (10(-8) M), natural cholecystokinin (CCK, 10(-8) M), and CCK octapeptide (10(-7) M), CCK preparations had no effect in the duodenum. Although tested over a wide range of concentrations, no effect on either duodenal or gastric HCO3- transport was observed with histamine, pentagastrin, tetragastrin, urogastrone, ACTH, bombesin, motilin, secretin, serotonin, somatostatin, substance P, or vasoactive intestinal peptide.
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PMID:Gastric and duodenal HCO3- transport in vitro: effects of hormones and local transmitters. 697 77

Cyclic AMP (cAMP) regulates many important physiological processes. Barbiturates influence cAMP regulation, possibly through effects on G proteins. This study used intact S49 mouse lymphoma cells to characterize the role of G proteins in the effect of barbiturates on cAMP regulation. cAMP accumulation was determined in intact S49 WT (wild-type) and S49 cyc- cells (the Gs alpha-deficient mutant) by measuring the conversion of [3H]-ATP to [3H]cAMP in cells preloaded with [3H]adenine. Pentobarbital enhanced cAMP accumulation in WT cells in the absence (basal) or presence of isoproterenol but had no effect on the EC50 for isoproterenol. This effect was dose dependent with a 50-60% enhancement at 2 mM pentobarbital. Pentobarbital did not affect forskolin-stimulated cAMP accumulation in WT cells. In cyc- cells, basal and forskolin-stimulated cAMP accumulation were stimulated only at the highest concentration of pentobarbital used (2 mM). Pentobarbital did not affect the inhibition of cAMP accumulation by somatostatin in WT cells, and pertussis toxin treatment of WT cells did not affect the action of pentobarbital on cAMP accumulation. Pentobarbital did not affect isoproterenol-stimulated adenylyl cyclase activity in whole-cell homogenates or membranes prepared from WT cells. The S-(-)-isomer of pentobarbital enhanced isoproterenol-stimulated cAMP accumulation more than the R-(-)-isomer. Phenobarbital and barbituric acid did not enhance isoproterenol-stimulated cAMP accumulation, whereas the anesthetic barbiturates hexobarbital, pentobarbital, and thiopental all enhanced activity. These results suggest that pentobarbital enhances cAMP accumulation in intact WT cells by a mechanism that is dependent on Gs alpha but independent of Gi.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anesthetic barbiturates enhance Gs alpha-dependent cyclic AMP production in S49 mouse lymphoma cells. 776 36

The mechanisms regulating the release of serotonin into the portal circulation as well as into the gastric lumen were studied in the isolated vascularly and luminally perfused rat stomach. Immunohistochemical study of the rat stomach showed that serotonin-containing enterochromaffin (EC) cells were densely packed in the antral mucosa, sparsely scattered in the corpus, and not found in the fundus. Such morphological findings suggest that serotonin detected in this study may have originated from antral EC cells. Luminal acidification stimulated the vascular release of serotonin but did not affect the luminal release of serotonin. The basal release of serotonin into the vasculature was 10 times higher than that into the gastric lumen at intragastric pH 2. The vascular release of serotonin is regulated by stimulation from cholinergic nicotinic mechanisms, whereas inhibitory neurotransmitters such as vasoactive intestinal peptide and NO are probably not involved. Somatostatin and peptide YY originating from endocrine cells may exert direct inhibitory effects, possibly via somatostatin and peptide YY receptors on the EC cells, and a cholinergic muscarinic mechanism may exert indirect effects on the vascular release of serotonin via the muscarinic receptor on the endocrine cells.
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PMID:Mechanisms in regulating the release of serotonin from the perfused rat stomach. 1135 2

1. Transport of a fluorescent somatostatin analogue (NBD-octreotide) across freshly isolated functionally intact capillaries from porcine brain was visualized by confocal microscopy and quantitated by image analysis. 2. Luminal accumulation of NBD-octreotide showed all characteristics of specific and energy-dependent transport. Steady-state luminal fluorescence averaged 2 - 3 times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. 3. The accumulation of NBD-octreotide in capillary lumens was inhibited in a concentration-dependent manner by unlabelled octreotide, by verapamil, PSC-833 and cyclosporin A, potent inhibitors of p-glycoprotein, and by leucotriene C(4), a strong modulator of Mrp2. Conversely, unlabelled octreotide reduced luminal accumulation of fluorescent BODIPY-verapamil on p-glycoprotein and of fluorescein-methotrexate, on Mrp2. None of the inhibitors used significantly reduced cellular accumulation of the fluorescent substrates. 4. Together, the data are consistent with octreotide being transported across the luminal membrane of porcine brain capillaries by both P-gp and Mrp2, providing further evidence that both transporters contribute substantially to the active barrier function of this endothelium.
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PMID:Permeability of porcine blood brain barrier to somatostatin analogues. 1187 40

Trimethyltin (TMT) is an organic metal known to induce neuronal degeneration in the hippocampus, and abnormal behavior characterized by seizures, increased aggression and memory deficits. We administered TMT to rats and studied the changes of neuropeptide Y (NPY) and somatostatin (SOM) in the hippocampus. Phenobarbital (PB) was administered as an anticonvulsant to assess the effect of seizures on neuropeptide expressions in both dorsal and ventral hippocampus. Histochemically, NPY-immunoreactivity increased 4 days after TMT treatment in the hilus of the hippocampus, then progressively decreased and dropped to a level below control 16 days after TMT treatment. Detection of NPY mRNA by in situ hybridization preceded the detection of NPY by immunohistochemistry. NPY mRNA signals increased in the hilus 2 days after TMT treatment. SOM-immunoreactivity also increased in the hilus of the hippocampus 2 days after TMT treatment, then decreased rapidly to a normal level. Similar changes in SOM mRNA were demonstrated by in situ hybridization. PB treatment significantly inhibited changes of NPY in terms of both immunoreactivity and mRNA expression; however, the same treatment failed to affect changes in SOM expression. This suggests that NPY and SOM act by different mechanisms in TMT-induced neurodegeneration.
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PMID:Neuropeptide Y and somatostatin participate differently in the seizure-generating mechanisms following trimethyltin-induced hippocampal damage. 1241 52


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