Disease relevance of Sst

• We now report the structural characterization of the rat somatostatin gene isolated from recombinant bacteriophage libraries prepared from rat liver DNA [1].
• The gene encoding rat somatostatin has been isolated from a lambda phage gene library [2].
• Forskolin (100 microM) as well as pretreatment of the cells with pertussis toxin significantly diminished the inhibitory effects of the three SS analogs and those of SS-14 and SS-28 to the same extent [3].
• Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism [4].
• In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by cultured cells from a human gastrinoma [3].
• We hypothesize that breathing requires preBötC Sst neurons and that their sudden depression can lead to serious, even fatal, respiratory failure [5].

Psychiatry related information on Sst

• Effect of food deprivation on rat gastric somatostatin and gastrin release [6].
• Somatostatin receptors in the nucleus accumbens selectively mediate the stimulatory effect of somatostatin on locomotor activity in rats [7].
• The effect of REM sleep deprivation on somatostatin and growth hormone-releasing hormone gene expression in the rat hypothalamus [8].
• Sleep deprivation increases somatostatin and growth hormone-releasing hormone messenger RNA in the rat hypothalamus [9].
• With doses higher than 10 micrograms (i.c.v.) SS provoked "barrel rotation", tremors and stereotyped behaviors [10].

High impact information on Sst

• Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133 [11].
• Administration of cortistatin depresses neuronal electrical activity but, unlike somatostatin, induces low-frequency waves in the cerebral cortex and antagonizes the effects of acetylcholine on hippocampal and cortical measures of excitability [12].
• Also, these phases of sleep are differentially sensitive to a number of endogenous neuropeptides and cytokines, including somatostatin, which has been shown to increase REM sleep without significantly affecting other phases [12].
• Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels [13].
• The neuropeptide somatostatin inhibits secretion from electrically excitable cells in the pituitary, pancreas, gut and brain [14].

Chemical compound and disease context of Sst

• The actions of progressive doses of intraperitoneally (IP) administered somatostatin-14 (SS-14) and -28 (SS-28) on gastric secretion (acid, pepsin) and mucosal blood flow (MBF) were studied in conscious gastric fistula rats both under basal conditions and under additional administration of pentagastrin [15].
• Percent weight gain, GHRH content, and SS content in control adolescent (8 weeks) and adult rats (6 months) were compared in normal rats administered supraphysiologic amounts of rat growth hormone (rGH) or in hypophysectomized rats receiving thyroxine and corticosterone with or without physiologic rGH replacement [16].
• METHODS: C6 rat glioblastoma cells were exposed to either IL-1 beta or its putative second messenger lysophosphatidylcholine (LPC) in the absence or presence of the inhibitory neurotransmitters somatostatin (SRIF) or gamma-aminobutyric acid (GABA) [17].
• Since mucosal proliferation was considered to contribute to healing of chronic gastroduodenal ulcerations, we designed the study to determine the interaction of GRF and somatostatin on the healing rate of acetic acid-induced chronic gastric and duodenal ulcers and on the growth of gastroduodenal mucosa in rats [18].
• Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h [19].

Biological context of Sst

• The somatostatin receptor type 2 analogue also inhibited gastrin-stimulated histamine release with a 50% inhibitory concentration (IC50) value of 2 x 10(-12) mol/L, whereas somatostatin 14 and the type 3 and 4 analogues showed IC50 values of 1 to 5 x 10(-9) mol/L [20].
• Previously, we have reported the isolation and nucleotide sequence of a cDNA derived from a rat medullary thyroid carcinoma that encoded preprosomatostatin , a 116-amino-acid precursor of somatostatin [1].
• Taken together, these results suggest that the low incidence of membrane-associated receptors observed in regions of somatodendritic sst2A labeling may be caused by downregulation of cell surface receptors by endogenous somatostatin, possibly through ligand-induced receptor internalization [21].
• The amino acid sequence of the tetradecapeptide somatostatin and of the amino-terminally extended form, somatostatin-28 was deduced from the nucleotide sequence of the complementary DNA [22].
• Analysis of rat DNA suggests that there may be restriction-site polymorphisms in or near the gene or that additional somatostatin-hybridizing sequences may exist in the genome [2].

Anatomical context of Sst

• CONCLUSIONS: The predominant somatostatin receptors on rat gastric ECL cells are of the somatostatin receptor 2 subtype; they inhibit histamine secretion by interfering with the gastrin-induced calcium signal [20].
• (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 [23].
• Double-labeling studies demonstrated that in the former but not in the latter regions, sst2A-immunoreactive somata and dendrites were heavily contacted by somatostatin axon terminals [21].
• Rats were killed after 7-28 days of treatment for diabetes, and somatostatin mRNA expression and pancreatic somatostatin content, CCK(B)R mRNA and protein expression evaluation in total pancreas and purified islets, and the cellular localization of somatostatin and CCK(B)R in islets was measured [24].
• A novel variant of ionotropic glutamate receptor regulates somatostatin secretion from delta-cells of islets of Langerhans [25].

Associations of Sst with chemical compounds

• Somatostatin also inhibited gastrin-mediated histamine release [26].
• The rate of gastrin release stimulated by carbachol was suppressed significantly by each dose of somatostatin examined (10(-8) M to 10(-4) M) [27].
• In dose-response studies, isoproterenol dose-dependently stimulated somatostatin secretion [6].
• These data suggest that GRF and somatostatin regulate the mitotic activity of GH-producing cells and that the effect of GRF is possibly mediated by cyclic AMP [28].
• Growth hormone-releasing factor increases somatostatin release and mRNA levels in the rat periventricular nucleus via nitric oxide by activation of guanylate cyclase [29].

Physical interactions of Sst

• Fractional reduction of somatostatin concentration interacted with rat growth hormone releasing hormone to titrate the magnitude of pulsatile growth hormone and prolactin release in perifusion [30].
• The aim of this study was to examine the potencies of several recently identified selective somatostatin (SRIF)-receptor ligands as inhibitors of electrogenic ion transport in the rat distal colonic mucosa with the view to identifying the SRIF receptor type involved [31].
• Analogues of somatostatin bind selectively to brain somatostatin receptor subtypes [32].
• These data suggest a SS receptor/G protein uncoupling as a result of binding of pentagastrin to gastrin receptors present in pancreatic acinar cell membranes [33].
• 125I-ET-1 binding to retinal particulate preparations was not inhibited by 1 microM concentrations of somatostatin, atrial natriuretic factor, brain natriuretic peptide, thyroid-stimulating hormone, growth hormone, or insulin [34].

Co-localisations of Sst

• Immunohistochemical studies indicated that AT2 receptors colocalized with somatostatin-producing cells in the endocrine pancreas [35].
• Substance P and calcitonin gene-related peptide which are colocalized in a proportion of the somatostatin neurons were unaffected [36].
• Somatostatin co-localizes with tyrosine hydroxylase in the nerve cells of discrete hypothalamic regions in rats [37].

Regulatory relationships of Sst

• Somatostatin inhibition of basal and carbachol-stimulated gastrin release in rat antral organ culture [27].
• While somatostatin blocked GRF-induced GH release, the augmented cAMP levels were only slightly reduced.(ABSTRACT TRUNCATED AT 400 WORDS)[38]
• Somatostatin inhibits interleukin 6 release from rat cortical type I astrocytes via the inhibition of adenylyl cyclase [39].
• Somatostatin and growth hormone inhibited inflammatory mediators and TNF alpha mRNA overexpressions, reduced the risk of MODS, corrected hypoalbuminemia, reversed negative nitrogen balance, and controlled the reduction of cell groups with functions and reasonably intervened SIRS caused by ANP [40].
• We propose that bFGF regulates the short term secretion and accumulation of SS and mediates rGRF-stimulated SS expression [41].

Other interactions of Sst

• Basal antral gastrin release was inhibited by somatostatin [27].
• The cholecystokinin B receptor (CCK(B)R) is localized on pancreatic endocrine somatostatin delta-cells [24].
• Somatostatin and the somatostatin receptor 2 are reciprocally controlled by calcineurin during cerebellar granule cell maturation [42].
• Although depolarizing concentrations of K+ (56 mM) did not increase IL-6 release, somatostatin release from the MBH was increased significantly [43].
• Our results show that the lateral CNA is a major source of CRF, NT, and SS terminals within the PBN [44].

Analytical, diagnostic and therapeutic context of Sst

• To investigate the functional significance of these distribution patterns, we examined the regional and cellular relationships between somatostatin axons and sst2A receptors in the rat CNS, using double-labeling immunocytochemistry [21].
• Light and confocal microscopy revealed a significant correlation (p < 0.02) between the distribution of somatodendritic sst2A receptor immunoreactivity and that of somatostatin terminal fields, both quantitatively and qualitatively [21].
• After treatment with L-glutamate, AMPA, or kainate, secretion of somatostatin from isolated islets was significantly stimulated under low-glucose conditions [25].
• Somatostatin cells from the canine gastric fundus were isolated by EDTA-collagenase dispersion and counterflow elutriation, and somatostatin-like immunoreactivity (SLI) release in response to SOS was measured by radioimmunoassay [45].
• The presence of SS-specific mRNA in 44-2C cells was shown morphologically by in situ hybridization [41].

References