Somatostatin, gastrointestinal peptides, and the carcinoid syndrome (original) (raw)
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Luminal gastric somatostatin-like immunoreactivity in response to various stimuli in man
Digestive Diseases and Sciences, 1986
This study investigates release of somatostatin-like immunoreactivity (SLI) into the gastric lumen of five healthy human subjects in response to pharmacological stimuli (pentagastrin and secretin) and physiolog!cal stimuli (sham feeding and intrajejuna! perfusion of elemental diet). Basal and poststimulation gastric juice aspirates were collected at 15-min intervals, extracted with acetone, and SLI determined by radioimmunoassay, with these results: (1) A considerable amount of SLI was secreted during the basal period. (2) Pentagastrin stimulated SLI release quickly and was associated with increased acid secretion. (3) Both secretin and sham feeding increased SLI only slightly. (4) During intrajejunal perfusion of the elemental diet, SLI increased significantly, was associated with decreased acid secretion~ and rapidly returned to basal level when elemental diet was replaced by saline. Basal levels of gastric luminal SLI thus showed distinct changes in response to each stimulus. Although the physiological action of luminal SLI remains to be studied, its levels may reflect gastric D-cell activities. Gastric D cells have been shown to have long processes, like neuronal processes, that come in contact with many effector cells. Other types of cells also appear to have contact with D cell processes on their terminals. Many D cell processes have contact with gastrin cells (G cells) in the antropyloric mucosa and with parietal cells in the oxyntic mucosa (1). Studie s have suggested that the activity of G cells and oxyntic cells of the stomach may be influenced by D cells via somatostatin. Somatostatin may be released into the interstitial Manuscript
British Journal of Pharmacology, 2005
Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst 1-5), of which sst 2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst 2-specific antagonist PRL-2903 was used. 2 Effects of PRL-2903 on acid secretion and release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the release of histamine and gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean7standard error of the mean (s.e.m.). 3 PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.677.5 to 3677114 nM at 50 mM PRL-2903. With 10 mM PRL-2903, venous histamine output increased from baseline 6.270.5 to 20.974.9 nmol h À1 ; P ¼ 0.008. The combination of 520 pM gastrin and 10 mM PRL-2903 increased venous histamine output from 41.777.3 nmol h À1 with gastrin alone to 95.279.8 nmol h À1 ; P ¼ 0.016. Further, 10 mM PRL-2903 increased acid output from baseline 8.571.8 to 37.4711 mmol h À1 ; P ¼ 0.017. When combined with 10 mM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4714.8 to 292764.2 nM; P ¼ 0.008, and gastrin concentration from 38.6713.1 to 95.8720.3 pM; P ¼ 0.037. 4 Endogenous somatostatin exerts a continuous restraint on histamine and gastrin release from the gastric mucosa and significantly reduces baseline acid secretion.
British journal of cancer, 1991
The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT f...
Central action of somatostatin analog, SMS 201-995, to stimulate gastric acid secretion in rats
Peptides
The effects of intracisternal and intravenous injections of the somatostatin analog, SMS 201-995, on gastric acid secretion were investigated in rats with pylorus ligation or gastric cannula. Intracisternal injection of SMS 201-995 induced a dose-related (0.1-0.3 microgram) and long-lasting stimulation of gastric acid output with a peak response at 3 h postinjection in conscious, pylorus-ligated rats. Intracisternal SMS 201-995 increased histamine levels in the portal blood, whereas plasma gastrin levels were not modified. Atropine, cimetidine and adrenalectomy abolished the stimulatory effect of intracisternal SMS 201-995 (0.3 microgram). SMS 201-995 (0.03 microgram), microinjected unilaterally into the dorsal vagal complex, increased gastric acid output in urethane anesthetized rats. SMS 201-995, injected intravenously at 0.5 microgram, did not alter gastric secretion, whereas higher doses (5-20 micrograms) resulted in a dose-related inhibition of gastric acid secretion in conscio...
Agents and Actions, 1977
The effect of cyclic somatostatin on pentagastrin-and histamine-stimulated gastric acid secretion in conscious cats was studied. Evidence is produced that somatostatin competitively inhibits pentagastrin-stimulated gastric acid secretion whereas it inhibits histamine-stimulated secretion by a mechanism which is not competitive in nature. The vagus nerves seem to be involved in the mode of action of somatostatin as the inhibitory effects are greater in vagotomized than in vagus intact animals.
British Journal of Clinical Pharmacology, 2001
Aims Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release. Methods Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day −1 s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured. Results After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment. Conclusions The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.
Evidence against prostaglandin-mediation of somatostatin-inhibition of gastric secretions
Regulatory Peptides, 1985
The inhibitory acivities 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.
The inhibitory acivities 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 in-domethacin, 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.