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 in five healthy volunteers whether the cholinergic pathway regulated the secretion of gastric intraluminal somatostatin-like immunoreactivity (SLI) in response to stimuli of pentagastrin infusion (0.9 micrograms/kg/h, intravenously) and sham feeding. We measured gastric secretory volume, hydrogen ion output, and SLI at base line, during pentagastrin infusion, after sham feeding, and after applications of atropine (0.0, 0.7, 7.0 micrograms/kg, intramuscularly) given before pentagastrin and sham feeding. The stimuli were given randomly, at separate times on different days. After each stimulus, eight 15-min gastric juice collections were made; samples were adjusted to pH 7, pepstatin-A and aprotinin were added, and samples were extracted with acetone to determine SLI by radioimmunoassay. Pentagastrin and sham feeding significantly increased gastric luminal SLI secretion, which appeared to correlate with the increases in volume and acid output. Atropine at 7 micrograms/kg significantly suppressed gastric volume, acid, and SLI outputs stimulated by sham feeding; however, responses to pentagastrin stimulation remained unchanged. To conclude, the cholinergic mechanism regulates gastric intraluminal SLI response to sham feeding but not to pentagastrin infusion.
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PMID:Mechanism of release of gastric luminal somatostatin-like immunoreactivity in response to pentagastrin and sham feeding in man. 343 15

A cyclic pseudohexapeptide analog of somatostatin, cyclo(Pro psi[ CH2S ]Phe-D-Trp-Lys-Thr-Phe) was synthesized by solid phase methods and diphenylphosphoryl azide ring closure. The resulting crystalline compound possessed 23% of the growth hormone inhibitory activity of the parent tetradecapeptide and approximately 6% of the activity of the all-amide cyclic hexapeptide analog in spite of the absence of one of two postulated intramolecular hydrogen bonds.
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PMID:Synthesis and biological activity of a cyclic pseudohexapeptide analog of somatostatin. 614 11

The role of endogenous prostaglandins in the physiologic regulation of gastric secretion is unclear. We evaluated the effect of indomethacin, an inhibitor of endogenous prostaglandin synthesis, on basal gastric secretion in humans using a two-component model for calculating gastric acid and bicarbonate secretion. After a control, gastric secretory study, 11 healthy volunteers were given 50 mg of indomethacin orally every 8 h for a total of 10 doses, after which the gastric secretory experiment was repeated. Indomethacin significantly (p less than 0.05) increased basal gastric juice volume, hydrogen ion concentration, osmolality, and acid output. Indomethacin increased acid secretion significantly (from 4.9 +/- 1.2 to 7.4 +/- 1.7 mmol/75 min, p less than 0.02) without affecting gastric bicarbonate secretion (control 2.7 +/- 0.8, indomethacin 3.0 +/- 0.7 mmol/75 min; p greater than 0.05). The increase in basal acid secretion after indomethacin administration was quite variable from subject to subject and was unaccompanied by significant changes in basal serum gastrin concentrations. Unlike basal acid secretion, indomethacin had no significant effect on acid secretion stimulated by intragastric infusion of homogenized food. Moreover, indomethacin did not prevent intravenous somatostatin 14 from inhibiting food-stimulated acid secretion, in contrast to a previous study in rats in which indomethacin blocked the inhibitory effect of somatostatin on acid secretion. Assuming the effect of indomethacin is due to reduced endogenous prostaglandin synthesis, we conclude that (a) in some individuals endogenous prostaglandins suppress basal acid secretion by a mechanism independent of the hormone gastrin; (b) endogenous prostaglandins play little, if any, role in the regulation of basal bicarbonate secretion by the stomach; and (c) endogenous prostaglandins do not regulate food-stimulated acid secretion, nor do they mediate the inhibitory effect of somatostatin on gastric acid secretion in humans.
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PMID:Effect of indomethacin on gastric acid and bicarbonate secretion in humans. 614 64

In guinea pig median eminences that were fixed with a glutaraldehyde paraformaldehyde mixtures, postfixed with osmium tetroxide, and embedded in araldite, immunocytochemical stainings for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and alpha 17-39 ACTH have been obtained on semithin sections. These positive reactions were obtained after araldite was removed with sodium methoxide and after treatment with hydrogen peroxide. These data suggest that osmium tetraoxide postfixation can be used for the detection of low molecular weight peptides such as LH-RH, somatostatin, and ACTH-like-peptides not only in the median eminence but also in the hypothalamus.
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PMID:Immunocytochemical demonstration of LH-RH, somatostatin, and ACTH-like peptide in osmium-postfixed, resin-embedded median eminence. 615 12

Preganglionic neurons in the lower lumbar spinal cord were labeled with horseradish peroxidase applied to the cut ends of the intermesenteric trunk in golden hamsters. A black granular reaction product was obtained in HRP-labeled cells by soaking spinal cord tissue in a cobalt chloride solution prior to treatment with diaminobenzidine (DAB) and hydrogen peroxide. Spinal cord sections containing labeled preganglionic neurons were processed with the immunoperoxidase (PAP) technique. Immunoreactive processes appeared as rust-brown beads. Concentrations of beaded processes exhibiting enkephalin-like, substance P-like (SPI) and somatostatin-like (SOMI) immunoreactivity were present around HRP-labeled preganglionic neurons in the intermediolateral cell column and in the dorsal commissural nucleus. Immunoreactivity was also present in the superficial dorsal horn, the dorsolateral funiculus and around the central canal. A prominent fiber system exhibiting SPI and SOMI extended from the ventral white matter to the ventral horn.
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PMID:Leu-enkephalin, substance P, and somatostatin immunohistochemistry combined with the retrograde transport of horseradish peroxidase in sympathetic preganglionic neurons. 618 92

Paired indirect immunoenzyme staining based on primary antisera from the same species was performed sequentially without intermediate antibody elution. The first antigen was labelled brown by an immunoperoxidase procedure (either the two-stage indirect method, the unlabelled antibody peroxidase-antiperoxidase method, or the avidin-biotin bridge method using diaminobenzidine (DAB) and hydrogen peroxide as the substrates. The second antigen was labelled blue by applying a two-stage indirect immuno-alkaline phosphatase procedure using naphthol AS phosphate and Fast Blue BB salt as the substrate. In this way, polyclonal mucosal immunocytes were revealed in distinctly contrasting colours when stained for kappa and lambda light chains. Glucagon and somatostatin (D) cells in human pancreatic islets, and gastrin and D cells in human gastric antral glands, were likewise clearly differentiated. Conversely, a mixed colour appeared in some immunocytes after staining for alpha and kappa chains. However, unbalanced colour mixing was sometimes difficult to interpret, and additional experiments demonstrated that unwanted interactions could take place between the two sequences of reagents if the density of the DAB deposits was insufficient. These pitfalls were incompatible with unequivocal double staining in the same cell. Nevertheless, paired staining could be conveniently applied with the described procedures when prior knowledge had established that the antigens in question were located in separate cells.
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PMID:Paired indirect immunoenzyme staining with primary antibodies from the same species. Application of horseradish peroxidase and alkaline phosphatase as sequential labels. 620 74

GABAA receptors mediate the inhibition of somatostatin gene expression and NMDA receptors mediate its stimulation. The aim of this study was to determine whether the two major neurotransmitters in the central nervous system (GABA and glutamate) could interact to control somatostatin mRNA content in primary cultures of hypothalamic neurons. Neurons were incubated for 15 min on days 3, 5, 7 or 11 of culture with Mg(2+)-free medium containing either NMDA (20 microM) or bicuculline (50 microM) to investigate the ontogenesis of somatostatin somatostatin secretion in response to NMDA and GABA. We found that NMDA significantly elicited somatostatin release from day 3, and bicuculline-induced release was observed from day 5. An ontogenetic study of somatostatin mRNA levels revealed that it steadily increased up to day 5 (6-fold) and a slight but nonsignificant decrease was observed on day 7 which stabilized until day 13. Experiments were thus carried out on day 11 of culture. Pharmacological manipulations of the two types of receptors (NMDA and GABAA) were performed to study the effect of the interaction on somatostatin mRNA accumulation. Time-course studies revealed the optimal time of action of the neurotransmitters (20 h). Our results demonstrated that bicuculline-induced mRNA accumulation was not additive with that elicited by NMDA after 20 h of incubation. In contrast, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d')cyclohepten-5,10-imine hydrogen (MK-801) at 10 microM completely abolished the stimulatory effect of bucuculline during the same time period. In addition, muscimol was unable to decrease somatostatin mRNA levels when NMDA receptors were blocked by MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABAA and NMDA receptor activation controls somatostatin messenger RNA expression in primary cultures of hypothalamic neurons. 784 37

1. Intracellular recordings were made from submucosal neurones in guinea-pig ileum. In some animals, the extrinsic (sympathetic) nerves to the submucosal plexus were severed 5-7 days previously. The actions of somatostatin and somatostatin analogues on membrane potential, membrane current and inhibitory postsynaptic potentials (IPSPs) were examined. 2. Somatostatin, somatostatin(1-28), [D-Trp8]somatostatin and the somatostatin analogue CGP 23996 all produced equivalent maximum hyperpolarizations or outward currents; half-maximal concentrations (EC50 values) were 9-11 nM. The somatostatin analogue MK 678 had an EC50 of 0.9 nM. Extrinsic sympathectomy did not alter concentration-response relations for somatostatin or its analogues. 3. Somatostatin (> 100 nM) produced hyperpolarization or outward current that declined almost completely during superfusion for 2-4 min; decline of the somatostatin current was exponential with a time constant of 30 s in the presence of 2 microM somatostatin. Desensitization was not altered by extrinsic denervation. 4. Recovery from desensitization was rapid and followed the time course of agonist wash-out. Forskolin, phorbol esters, dithiothreitol, hydrogen peroxide, concanavalin A, or reducing temperature from 35 to 29 degrees C did not alter the time course, degree of, or recovery from desensitization. 5. The somatostatin-induced desensitization was of the homologous type; no cross-desensitization to opiate or alpha 2-adrenoceptor agonists (which activate the same potassium conductance) occurred. 6. Somatostatin desensitization did not alter the adrenergic IPSP seen in sympathetically innervated preparations but abolished the non-adrenergic IPSP recorded from normal preparations and from preparations in which the extrinsic sympathetic nerve supply had been surgically removed. 7. The selective blockade of the non-adrenergic IPSP by the homologous-type somatostatin desensitization characterized in the present study provides strong support for the hypothesis that somatostatin is the neurotransmitter underlying the non-adrenergic IPSP in both normal and extrinsically denervated submucosal neurones.
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PMID:Somatostatin-mediated inhibitory postsynaptic potential in sympathetically denervated guinea-pig submucosal neurones. 790 23

Sixteen healthy male volunteers participated in a randomized, double blind, parallel groups study. Subjects received either 1 or 5 mg SDZ CO 611 (a new, orally active somatostatin analog) twice daily over a 14-day period and acted as their own controls. Gastric emptying of 99mTc and mouth to cecum transit time, as measured by the breath hydrogen technique, after a mixed meal containing lactulose and 99mTc-diethylenetriaminepentaacetate, were assessed once before, twice during, and once after the period of study medication. Gastric emptying of 99mTc was significantly accelerated by the higher dose of SDZ CO 611, whereas mouth to cecum transit time was prolonged by the drug in a dose-dependent manner. Both doses of SDZ CO 611 led to suppression of the fasting level and postprandial release of several gastrointestinal and pancreatic hormones. This effect was more marked in those subjects taking 10 mg/day of the study medication. Motilin and pancreatic polypeptide were the most sensitive to the inhibitory actions of the analog. Glucose tolerance was significantly impaired by the 10-mg dose of the drug. We conclude that this new, orally active derivative of somatostatin is as effective on the gastrointestinal tract as the sc somatostatin analog octreotide. It would, therefore, be a useful advance in the treatment of gastroenteropancreatic tumors.
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PMID:Effect of a new oral somatostatin analog (SDZ CO 611) on gastric emptying, mouth to cecum transit time, and pancreatic and gut hormone release in normal male subjects. 790 79

Gastric acid secretion is precisely regulated by neural (acetylcholine), hormonal (gastrin), and paracrine (histamine; somatostatin) mechanisms. The stimulatory effect of acetylcholine and gastrin is mediated via increase in cytosolic calcium, whereas that of histamine is mediated via activation of adenylate cyclase and generation of cAMP. Potentiation between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways and/or the ability of gastrin and acetylcholine to release histamine from mucosal ECL cells. The prime inhibitor of acid secretion is somatostatin. Its inhibitory paracrine effect is mediated predominantly by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+,K(+)-ATPase, the proton pump of the parietal cell. Precise information on the mechanisms involved in gastric acid secretion and the identification of specific receptor subtypes has led to the development of potent drugs capable of inhibiting acid secretion. These include competitive antagonists that interact with stimulatory receptors (e.g. muscarinic M1-receptor antagonists and histamine H2-receptor antagonists) as well as non-competitive inhibitors of H+,K(+)-ATPase (e.g. omeprazole). The histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine and roxatidine acetate) continue as first-line therapy for peptic ulcer disease and are effective in preventing relapse. Although they are generally well tolerated, histamine H2-receptor antagonists may cause untoward CNS, cardiac and endocrine effects, as well as interfering with the absorption, metabolism and elimination of various drugs. The dominance of the histamine H2-receptor antagonists is now being challenged by omeprazole. Omeprazole reaches the parietal cell via the bloodstream, diffuses through the cytoplasm and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. Here, it covalently binds to H+,K(+)-ATPase, the hydrogen pump of the parietal cell, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main potential drawback to its use is its extreme potency which sometimes leads to virtual anacidity, gastrin cell hyperplasia, hypergastrinaemia and, in rats, to the development of carcinoid tumours. The cholinergic receptor on the parietal cell has recently been identified as an M3 subtype and that on postganglionic intramural neurones of the submucosal plexus as an M1 subtype.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacology of gastric acid inhibition. 809 11


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