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)

Sprague-Dawley rats treated with placebo, parenteral indomethacin, or oral prostaglandin E2 for six days were given an intraperitoneal injection of [3H] methyl-thymidine and killed at 45 min and 96 hr after labeling. Treatments were continued until death. The dpm/DNA index was determined in mucosal scrapings of the stomach, duodenum, and jejunum and used to estimate DNA synthesis (45 min) and the clearance of labeled cells (96 hr). Indomethacin increased the DNA synthesis in both the duodenal and jejunal mucosa (P less than 0.05). In comparison to the controls, the clearance of labeled cells from the antral, duodenal, and jejunal mucosa was accelerated by indomethacin treatment, whereas the elimination of labeled cells from the antral and jejunal mucosa was slowed by PGE2 treatment (P less than 0.05). DNA synthesis of the antral mucosa was significantly reduced by PGE2 (P less than 0.05). The cyclooxygenase blocker did not affect the cell kinetic parameters of the oxyntic mucosa. The plasma levels of somatostatin were significantly higher both in PGE2- and indomethacin-treated rats than in controls (P less than 0.05). It is concluded that indomethacin treatment increases the cell losses from the epithelial surface, which in turn trigger a compensatory trophic reaction. It is suggested that an important physiological action of endogenous prostaglandins is to regulate the outflow of cells from the superficial zones of the epithelium. Finally, this study disclosed the presence of hitherto unknown regulatory mechanisms that promote cell proliferation in the gastrointestinal mucosa despite inhibition of the synthesis of endogenous prostaglandins.
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PMID:Indomethacin accelerates clearance of labeled cells and increases DNA synthesis in gastrointestinal mucosa of the rat. 134 16

We have recently shown that glutamate exerts a stimulatory action on somatostatin secretion in cortical neurons essentially through NMDA receptor sites. Here, we investigated whether arachidonic acid release could be modified after NMDA receptor activation in cortical neurons in primary culture. We also studied whether pharmacological manipulation of phospholipase A2 could modify somatostatin release. We found that both glutamate and NMDA (N-methyl-D-aspartate) stimulated [3H]arachidonic acid release. NMDA-evoked arachidonic acid release was inhibited by MK-801 and TCP (two NMDA receptor-type antagonists), or by mepacrine, an inhibitor of phospholipase A2. NMDA-induced somatostatin release was inhibited by MK-801, mepacrine and by another phospholipase A2 inhibitor, p-bromophenacylbromide (pBPB). However, responses to NMDA were unaffected by H7, NDGA (nordihydroguaiaretic acid), indomethacin or by RHC 80267 (inhibitors of protein kinase C, lipooxygenase, cyclooxygenase and diacylglycerol lipase, respectively). Mepacrine (greater than or equal to 100 microM) decreased NMDA-stimulated phosphatidylinositol (PI) hydrolysis and at higher concentrations (250 microM) was also able to inhibit basal release whereas pBPB had no effect in the range of concentrations tested. Neomycin (which inhibits phosphatidylinositol metabolism by binding strongly and selectively to inositol phospholipids) reduced by 30% the NMDA-stimulated somatostatin release, although chronic treatment of neurons with the phorbol ester 12-myristate, 13-acetate (PMA) had no effect on this response. Melittin, an activator of phospholipase A2, was able to stimulate both arachidonic acid release and somatostatin secretion. High-performance liquid chromatography (HPLC) analysis of tritiated metabolites released from cortical neurons under basal or NMDA-stimulated conditions revealed that [3H]arachidonic acid was the only metabolite detectable. Furthermore, external addition of arachidonic acid increased somatostatin secretion. Our results show a correlation between the two parameters studied.
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PMID:NMDA receptor activation stimulates phospholipase A2 and somatostatin release from rat cortical neurons in primary cultures. 135 46

There is convincing evidence from in vitro studies that prostaglandins interfere with the gastrin histamine regulation of gastric acid secretion in an opposing manner. They can inhibit the action of histamine on the parietal cell when given as single-dose treatment. Conversely, when given at high doses, they liberate endogenous histamine, probably from nonparietal cells. In in vivo experiments prostaglandins are potent inhibitors of acid secretion when studied with single-dose treatment but are capable of stimulating basal acid secretion when chronically applied to rats. Studies performed in whole animal preparations on the effect of cyclooxygenase inhibitors have not fully clarified which of these two histamine-modulating effects of prostaglandins is of prime physiologic significance but favour suppression of histamine activity with subsequent acid inhibition. It appears that somatostatin release is the mechanism through which prostaglandin can simultaneously inhibit acid secretion and release plasma gastrin. At least in the rat, the pattern of plasma gastrin and somatostatin release is, similarly to acid secretion, partly reversed during prolonged prostaglandin treatment.
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PMID:Aspects of the role of prostaglandins in gastrin histamine regulation of gastric acid secretion. 167 23

The epoxyeicosatrienoic acids (EETs) were discovered as products of a cyclooxygenase/lipoxygenase-independent, cytochrome P-450 catalyzed metabolism of arachidonic acid (AA) termed the "epoxygenase" pathway. The rat hypothalamus is able to synthesize EETs from exogenous AA, and 5,6-EET has been found to release the neuropeptide somatostatin (SRIF) from hypothalamic nerve terminals of the median eminence (ME). In the present study, hypothalami from male rats were examined for the presence of endogenous EETs, using chemical, chromatographic, and mass spectral analysis procedures. The samples were initially separated in a C18 Sepralyte column, fractionated on TLC plates, and purified by reverse phase HPLC. Thereafter, they were esterified (pentafluorobenzyl esters) and subjected to negative ion chemical ionization/gas chromatography (GC)/mass spectral (MS) analysis. The GC retention time and the MS fragmentation patterns revealed the presence of a mixture of 8,9-, 11,12- and 14,15-EETs; instability of 5,6-EET during the isolation protocol precluded its identification. Total hypothalamic EET concentration was estimated to be 120 ng/g wet tissue. The 8,9-regiosomer released SRIF from ME nerve terminals with an ED50 of 5 x 10(-12) M; Dopamine (DA) and the D2 receptor agonist PPHT, but not the D1 receptor agonist SKF-38393, induced SRIF release from the ME. This effect was blocked by clotrimazole and ketoconazole, two inhibitors of microsomal cytochrome P-450 function and AA epoxygenase in particular. In contrast, the inhibitors failed to affect the increase in SRIF release induced by 8,9-EET. These results indicate that: 1) in addition to cyclooxygenase and lipoxygenase products, epoxygenase metabolites of AA are endogenous compounds of the hypothalamus, and 2) EETs may mediate the increase in SRIF release from hypothalamic neurons induced by the interaction of DA with D2 receptors.
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PMID:Epoxygenase products of arachidonic acid are endogenous constituents of the hypothalamus involved in D2 receptor-mediated, dopamine-induced release of somatostatin. 196 82

The possible involvement of arachidonic acid (AA) release in growth-hormone-releasing factor (GRF)-induced somatostatin (SRIF) release from the median eminence (ME) of the hypothalamus was evaluated in adult male rats using an in vitro incubation system. The MEs were preincubated with [14C]-AA, then washed and incubated with vehicle or test agents, and the release of SRIF and [14C]-AA into the medium was measured. In the experiments designed only to determine SRIF release, the MEs were first preincubated for 30 min. The medium was then discarded and replaced with fresh buffer or test substances and incubated for 10, 20 and/or 30 min. GRF (10(-10) M) stimulated both AA and SRIF release significantly within 20 min, with maximum release occurring at 30 min. The stimulatory effect of GRF on AA release was coincident with the release of SRIF. A phospholipase A2 inhibitor (10(-6) M, quinacrine) completely abolished the stimulatory effect of GRF on both AA and SRIF release. The release of SRIF induced by GRF was also inhibited by both indomethacin (10(-6) M, a cyclooxygenase inhibitor) and metyrapone (10(-6) M, a cytochrome P-450 inhibitor). On the other hand, nordihydroguaiaretic acid (10(-6) M, a lipoxygenase inhibitor) had no effect on GRF-evoked SRIF release. The data presented here suggest that an important GRF-mediated event leading to SRIF secretion is an elevated release of AA from ME fragments in vitro. In conclusion, our data are suggestive that the stimulatory effect of GRF on SRIF release is due, in part, to the release and subsequent metabolism of AA to one or more metabolites.
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PMID:Role of arachidonic acid or its metabolites in growth-hormone-releasing factor-induced release of somatostatin from the median eminence. 197 95

The effects of different prostanoids on parietal cell activity and glandular histamine (Hi) release were examined in isolated rabbit gastric glands. [14C]aminopyrine accumulation and glandular oxygen consumption were used as indices of parietal cell activity, and Hi was determined fluorophotometrically in the supernatant of the glandular suspensions. Both prostaglandins (PG) E2 and E1 dose dependently (10(-8) and 10(-6) M) increased the release of endogenous Hi. Carbacyclin was less effective and PGF2 alpha was almost without effect. Hi release induced by acetylcholine (Ach) and pentagastrin (Pg) was markedly potentiated in the presence of PGE2 (10(-8) to 10(-5) M). The Ach-induced sti ulation of Hi release was also potentiated by arachidonic acid (10(-5) M), an effect that was inhibitable by the cyclooxygenase inhibitor meclofenamate (3 X 10(-5) M). Somatostatin partially inhibited the response to Pg (3 X 10(-9) M) in combination with PGE2 (10(-5) M). Atropine (10(-5) M) strongly reduced the response elicited by Ach (3 X 10(-6) M) combined with PGE2 (10(-6) M). All prostanoids inhibited Hi (10(-4) M)-induced parietal cell activity in a dose-dependent manner (60-70%) but displayed different potency. The stimulatory response to Ach (3 X 10(-6) M) or Pg (3 X 10(-9) M) in combination with isobutylmethylxanthine (IBMX, 10(-5) M) was inhibited by PGE2 in a dose-dependent fashion. PGE2 (10(-6) M) was considerably more effective than cimetidine (10(-5) M) in inhibiting IBMX (10(-4) M)-stimulated oxygen consumption, and the remaining IBMX-PGE2 response (approximately 40%) was dose dependently (10(-8) to 10(-5) M) inhibited by cimetidine. Addition of Hi (10(-7) to 4 X 10(-7) M) or Pg (3 X 10(-10) to 3 X 10(-9) M) counteracted the PGE2 inhibition of the IBMX response. In addition, IBMX (10(-4) M) combined with PGE2 (10(-6) M) gave rise to a threefold increase in Hi release. These results suggest that prostaglandins have two opposing effects, i.e., liberation of endogenous Hi and inhibition of the action of Hi on the parietal cell.
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PMID:Prostaglandin interaction with histamine release and parietal cell activity in isolated gastric glands. 242 53

Cachectin (tumor necrosis factor) is a powerful macrophage hormone released during infection, which circulates in blood to produce diverse effects in the organism. We examined the effect of cachectin on release of anterior pituitary hormones from either hemipituitaries or dispersed pituitary cells incubated in vitro. The action of cachectin on dispersed cells was demonstrable only after 2 hr of incubation. With this incubation time, the protein produced a dose-related stimulation of release of adrenocorticotropin (ACTH), growth hormone (GH), and thyrotropin (TSH), but not of prolactin (Prl), from both hemipituitaries and dispersed cells. The doses required for stimulation were low in the case of hemipituitaries, usually of the order of 10(-12) M, whereas they were higher by one or two orders of magnitude with the dispersed pituitary cells. This may be related either to loss of receptors for the protein during the dispersion procedure or to the fact that in the hemipituitary system cell interactions are facilitated because the cells are close to each other. In the dispersed cell system cachectin evoked a dose-related decrease in cyclic AMP content. Incubation with somatostatin lowered the cyclic AMP content of the cells and depressed GH output without altering output of TSH or Prl. When somatostatin and cachectin were incubated together with the cells, the suppression of cyclic AMP production was abolished; TSH and Prl release were stimulated, but the action of cachectin to stimulate GH release was blocked. The stimulation of Prl release by cachectin in the presence of somatostatin may be related to the elevation of cyclic AMP, a known stimulator of Prl release. The cyclooxygenase inhibitor indomethacin nearly completely blocked the stimulatory effect of cachectin on release of GH and TSH from dispersed pituitary cells but had only a slight and nonsignificant attenuating effect on its ACTH-releasing action. These results suggest that at least part of the stimulatory action of the peptide on pituitary hormone release is brought about by prostaglandins. The failure of indomethacin to block the release of ACTH induced by cachectin suggests that other mechanisms may be involved in the release of ACTH induced by this peptide. Since the concentrations of cachectin required to stimulate pituitary hormone release are similar to those that are encountered in plasma during infection, it is likely that this direct pituitary action has pathophysiological significance.
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PMID:Cachectin alters anterior pituitary hormone release by a direct action in vitro. 256 80

Rat anterior pituitaries were incubated over a 3-h period. Both PGE2 and GH were increased by GRF in a concentration-related manner (ED50: 3.5 nM and 6.5 nM, respectively). A significant correlation (r = 0.88, n = 127) was observed between GH and PGE2 release over the range of GRF concentrations tested. Among the five prostanoids analyzed, only PGE2 was selectively increased. Somatostatin lowered GH release, without any effect on PGE2 production. Indomethacin (Id) and Aspirin reduced significantly PGE2 synthesis and GRF-induced GH release. The inhibitory effect of Id was counteracted by addition of PGE2 to the medium. GRF and PGE2, at maximal concentrations, had a partial additive effect on GH release. The increase in PGE2 production and the reduced GH release in the presence of cyclooxygenase inhibitors suggest that PGE2 is involved in GRF-induced GH release.
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PMID:Growth hormone-releasing factor (GRF) stimulates PGE2 production in rat anterior pituitary. Evidence for a PGE2 involvement in GRF-induced GH release. 285 4

The inhibitory activities of somatostatin and PGE2 against pentagastrin-stimulated gastric acid and pepsin secretions were investigated, with and without pretreatment with the cyclooxygenase inhibitor indomethacin, in conscious cats prepared with gastric fistulae. Somatostatin was a potent inhibitor of acid secretion in both vagus intact and vagotomized animals, and its effect was not diminished by indomethacin pretreatment. Somatostatin inhibition of pepsin secretion was diminished after indomethacin, but a similar effect was noted with exogenous PGE2, suggesting a mechanism unrelated to inhibition of prostaglandin synthesis. It is concluded that there is no evidence to implicate endogenous prostaglandins in somatostatin inhibition of feline gastric exocrine secretions.
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PMID:Evidence against prostaglandin-mediation of somatostatin-inhibition of gastric secretions. 285 41

GRF, a specific stimulator of GH release, increased in a concentration- and time-dependent manner pituitary [3H]-arachidonate levels in vitro. This effect was antagonized by 100 nM somatostatin. Exogenous arachidonate also stimulated GH release in vitro. Quinacrine, a phospholipase A2 inhibitor, reduced both basal and GRF-stimulated free arachidonate levels as well as GH release. The cyclooxygenase inhibitor indomethacin was ineffective, while BW755c, which also inhibits the lipoxygenase pathway, produced a further increase in the levels of the fatty acid stimulated by GRF and potently reduced GH release. These results provide additional evidence for the involvement of arachidonate metabolism in the hormone-releasing effect of GRF at the somatotroph.
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PMID:Growth hormone releasing factor (GRF) increases free arachidonate levels in the pituitary: a role for lipoxygenase products. 286 52


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