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)

Somatostatin has been shown to lower plasma levels of various hormones and growth factors involved in regulation of the growth of human breast cells. In the present study we examined the ability of the somatostatin octapeptide analog BIM23014 to modulate the in vitro growth of five human breast cell lines: HBL100, Hs578T, MDAMB231, T47D, and MCF7. BIM23014 inhibited the growth of the two steroid-dependent cell lines, MCF7 and T47D, in a dose-related manner. This inhibitory effect was only observed when MCF7 and T47D cells were cultivated in medium containing steroid-depleted serum. The growth of a MCF7 variant capable of growth in serum-free medium was also inhibited by BIM23014, indicating that serum factors are not required for this inhibition. In the serum-free medium, the addition of estradiol before or during treatment with BIM23014 abolished its inhibitory effects on cell growth. The studies including time course, competitive inhibition, and cross-linking of iodinated BIM23014 to its receptor revealed a specific binding on MCF7 cells and showed a single 57,000 mol wt protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results support the hypothesis that BIM23014 inhibits the growth of steroid-receptor positive cells of human breast cancers through its own receptor in estradiol-free conditions.
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PMID:Growth of human breast cancer cell lines is inhibited by the somatostatin analog BIM23014. 205 92

To determine the time onset of the growth hormone (GH) alteration in the genetically obese rat, we studied the in vivo and in vitro rat growth hormone releasing factor (rGRF(1-29)NH2)-induced GH secretion in 6- and 8-week-old lean and obese male Zucker rats. Under sodium pentobarbital anesthesia, rGRF(1-29)NH2 (GRF) was injected intravenously at two doses: 0.8 and 4.0 micrograms/kg b.w. Basal serum GH concentrations were similar in lean and obese age-matched animals. The GH response to both GRF doses tested was unchanged in 6-week-old obese rats as compared to their lean litter mates. In contrast, a significant decrease of the GH secretion in response to 4.0 micrograms/kg b.w. GRF was observed in the 8-week-old obese rats. The effect of GRF (1.56, 6.25 and 12.5 pM) was further studied in vitro, in a perifusion system of freshly dispersed anterior pituitary cells of lean and obese Zucker rats. Basal GH release was similar in the 6-week-old animal group. In contrast, it was significantly decreased in 8-week-old obese rats as compared to their lean litter mates. Stimulated GH response to 1.56 and 6.25 pM GRF was significantly greater in the 6-week-old obese group than in the age-matched control group. In contrast, the GH response to all GRF concentrations tested was significantly decreased in the 8-week-old obese rats as compared to their respective lean siblings. In 8-week-old obese rats, a decrease of GH pituitary content and an increase of hypothalamic somatostatin (SRIF) concentration were observed. Insulin and free fatty acid serum were significantly increased in 8-week-old obese rats. In contrast, lower insulin-like growth factor I serum levels were observed in the obese animals as compared to their lean litter mates. Finally, to further clarify the role of the periphery in the inhibition of GH secretion observed in the 8-week-old fatty rats, we exposed cultured pituitary cells of 8-week-old lean animals to 17% serum of their obese litter mates. A significant decrease of GRF-stimulated GH secretion of lean rat pituitary cells exposed to the obese serum was noted (P less than 0.05). This study demonstrates that, in the obese Zucker rat, an alteration of the GH response to GRF is evident by the 8th week of life. This defective GH secretion could be related to peripheral and central abnormalities.
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PMID:Dynamic of the GRF-induced GH response in genetically obese Zucker rats: influence of central and peripheral factors. 213 33

Suppression of growth hormone by means of somatostatin has been suggested as a possible adjunct therapy in Type 1 diabetes. To assess the acute effect of the somatostatin analogue SMS 201-995 on kidney function in uncomplicated Type 1 diabetes, 13 normoalbuminuric, normotensive diabetic patients were investigated before and during IV infusion of SMS 201-995 (8 micrograms h-1). A control experiment with infusion of carrier only was also performed. The SMS infusion induced a reduction in the glomerular filtration rate (clearance of 125I-iothalamate) and renal plasma flow (131I-hippuran) from 140 +/- 15 (mean +/- SD) and 550 +/- 69 to 131 +/- 14 (2p less than 0.005) and 492 +/- 73 ml min-1 1.73-m-2 (2p less than 0.001), while filtration fraction and total renal resistance rose (both 2p less than 0.001). Urinary albumin excretion rate, blood pressure, and blood glucose concentration were unchanged. Plasma growth hormone and glucagon were significantly suppressed. The reduction in glomerular filtration rate and renal plasma flow correlated with the fall in glucagon concentration (r = 0.57, 2p = 0.04, and r = 0.63, 2p = 0.02). The urinary flow rate was markedly reduced, urine osmolality increased, and fractional excretion of sodium, calcium, and phosphate were reduced. Arginine vasopressin, atrial natriuretic peptide, angiotensin II, and aldosterone were unchanged by the SMS infusion. Thus SMS 201-995 acutely reduces glomerular filtration rate and renal plasma flow in uncomplicated Type 1 diabetes and has an antidiuretic effect. The effects may be related to suppression of glucagon secretion.
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PMID:Acute effects of a somatostatin analogue on kidney function in type 1 diabetic patients. 214 82

Somatostatin is widely distributed within the nervous system and the gastrointestinal tract. Gastrointestinal actions of somatostatin include inhibition of hormone release, reduction of pancreatic secretion, inhibition of motility, and reduction of blood flow. The purpose of this study was to investigate the role of somatostatin and its analogue octreotide on water and electrolyte transport in the small intestine. Rabbit ileal segments (n = 17) were harvested and arterially perfused ex vivo with a nonrecirculating oxygenated sanguineous solution. The lumen was perfused with an isotonic solution containing carbon 14-labeled polyethylene glycol. Net fluxes of water, Na+, and Cl- were calculated for three 20-minute periods designated basal, drug infusion, and recovery. Three groups were studied: somatostatin at 10(-6) mol/L (n = 5), somatostatin at 10(-5) mol/L (n = 5), and octreotide at 10(-5) mol/L (n = 7). Somatostatin at 10(-5) mol/L yielded a proabsorptive effect on the flux of water and electrolytes. Octreotide at 10(-5) mol/L caused a significant (p less than 0.05) proabsorptive response in the fluxes of water, sodium, and chloride during the period of drug infusion, which returned to basal secretory levels during the recovery period. This proabsorptive effect occurred without alterations in vascular resistance and necessarily was independent of systemic hormone interaction, supporting a direct effect of octreotide on intestinal ionic transport.
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PMID:Direct proabsorptive effect of octreotide on ionic transport in the small intestine. 224 38

The recent study has demonstrated the presence of somatostatin (SRIF) secretory cells in the rat glomerulus. Because of the polyvalent actions of this peptide, SRIF may play some roles in the evolution of chronic renal failure. The present study evaluated the effects of a long acting SRIF analogue, SMS 201-995 on the progression of renal failure in 3/4 nephrectomized (NPX) rats. Animals were divided into four groups; (1) normal control (C) (n = 9), (2) NPX-C (n = 10), (3) NPX treated with SMS 201-995 (0.5 micrograms/day) (NPX-0.5) (n = 9) and (4) NPX with SMS 201-995 (5.0 micrograms/day) (NPX-5.0) (n = 9). This drug was subcutaneously given daily for 6 weeks. Periodic observations were done at 0, 3 and 6 weeks. Both hematocrit and systolic blood pressure showed significant fall and rise, respectively, in NPX rats compared with C at 3 and 6 weeks. Also both serum creatinine and blood urea nitrogen in these groups elevated significantly at 3 and 6 weeks compared with C. Not significant changes were observed in the 24-h urine volume among the NPX rats. At 6 weeks, the urinary protein excretion in NPX-5.0 was significantly less than those in NPX-C and NPX-0.5 rats. Urinary sodium excretion in NPX-5.0 was significantly lower than that in NPX-C. Histologic examination of the kidney showed less proliferation of mesangial cells in NPX-5.0 than NPX-C. These results suggest that SMS 201-995 may limit the rate of progression of chronic renal failure in this experimental model.
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PMID:Effects of chronic administration of somatostatin analogue SMS 201-995 on the progression of chronic renal failure in subtotal nephrectomized rats. 227 32

We have attempted to define the nature of insulin secretory defect(s) in aged animals. In these studies, pancreatic islets were isolated from 2- and 18-mo-old Fischer 344 rats. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors to the surface membrane. Section vesicle lysis was studied by measuring insulin release into the incubation media. Submaximal and maximal glucose-induced insulin secretion was significantly greater in islets isolated from younger rats (P less than 0.01). SRIF receptor recruitment was stimulated by glucose in both younger and older Fischer 344 rats. However, an increase in SRIF receptor recruitment was reduced in islets isolated from older animals (from 2.14 +/- 0.4 to 4.6 +/- 0.4 fmol/10 islets) (P less than 0.01) as compared with islets from younger animals (from 2.6 +/- 0.2 to 6.2 +/- 0.4 fmol/10 islets). When secretion vesicle lysis was inhibited by the presence of sodium isethionate in the incubation media, glucose (300 mg/dl) failed to stimulate secretion vesicle margination to the plasma membrane. In contrast, glyburide (0.6 micrograms/ml) continued to stimulate directly secretion vesicle margination in islets from aged animals (from 2.1 +/- 0.3 to 6.0 +/- 0.3 fmol/10 islets). We conclude that glucose-induced margination of secretion vesicles at the plasma membrane is impaired by the aging process. This impairment results in lower submaximal and maximal insulin secretory response to glucose. The fact that glyburide is capable of stimulating secretion vesicle margination suggests that glucose signal recognition and/or stimulus-secretion coupling may be the locus of impairment in the process of insulin secretion in older animals.
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PMID:The nature of insulin secretory defect in aging rats. 241 20

We have examined the effect of exogenous insulin on secretion vesicle margination and secretion vesicle lysis in isolated perifused rat pancreatic islets. Recruitment of somatostatin (SRIF) receptors to the plasma membrane was used as a marker of secretion vesicle margination, whereas insulin release reflected the process of secretion vesicle lysis. A newly designed perifusion protocol allows one to interrupt intermittently either secretion vesicle margination or secretion vesicle lysis. Islets were initially perifused with glucose (30, 100, 165, 200, or 300 mg/dl) in the presence of sodium isethionate. Sodium isethionate inhibits secretion vesicle lysis, but not the recruitment of SRIF receptors. Thus, the margination of secretion vesicles to the surface membrane continued without their lysis. Sodium isethionate was then removed, and islets were challenged with 400 microM isobutylmethylxanthine (IBMX). In the islets perifused with high glucose concentrations, IBMX lysed a greater number of vesicles and caused enhanced release of insulin. The presence of exogenous insulin during the initial phase of secretion vesicle margination did not affect subsequent IBMX-induced insulin secretion from the islets perifused with low glucose concentrations (30 or even 100 mg/dl). When the glucose concentration was increased to 165, 200, or 300 mg/dl, insulin significantly diminished IBMX-induced insulin release. In separate experiments, increasing concentrations of insulin (50, 100, and 200 microU/ml) reduced glucose-induced recruitment of SRIF receptors in a dose-dependent manner. Our observations strongly suggest the existence of a well balanced relationship between ambient glucose and insulin concentrations in terms of their positive and negative feedback actions on insulin release. Their influences seem to be exerted at the level of secretion vesicle margination at the plasma membrane.
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PMID:Feedback inhibition of insulin on insulin secretion in isolated pancreatic islets. 241 17

A new sequential gating perifusion technique was employed to investigate secretion vesicle margination and granule lysis in islets isolated from 2- and 18-month-old Fischer 344 rats. The technique is based on sequential perifusion (periods A, B, and C) of isolated islets with glucose (30, 165, or 300 mg/dl) in the presence of sodium isethionate, an inhibitor of granule lysis, followed thereafter by trifluoperazine, an inhibitor of secretion vesicle margination, and glucose (300 mg/dl) or isobutylmethylxanthine (IBMX; 400 microM). When glucose was employed during period A to marginate secretion vesicles to the plasma membrane, subsequent glucose- and IBMX-induced insulin release (period C) was depressed in islets from 18-month-old rats [maximal increase above the basal rate of release (delta max), 9 +/- 2 nU/micron X min] compared to that in the 2-month-old animals (delta max, -19 +/- 3 nU/micron X min). With glyburide (400 microM) used to induce secretion vesicle margination, glucose- and IBMX-induced insulin release was the same in young and old animals (delta max, 14 +/- 3 and 15 +/- 3 nU/micron X min, respectively). Insulin release was then studied as a function of secretion vesicle margination at the plasma membrane by measuring somatostatin (SRIF) receptor recruitment. The islets from older animals must be stimulated with 300 mg/dl glucose to attain the same level of SRIF binding as in islets isolated from younger animals stimulated with 150-165 mg/dl glucose. Insulin release per unit SRIF binding was identical in young and old animals (65 and 69 nU/liter fmol SRIF binding), indicating normal lysis of marginated secretion granules. These studies implicate glucose-induced secretion vesicle margination as the site of impairment in age-related insulin release.
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PMID:Insulin secretion in aging: studies with sequential gating of secretion vesicle margination and lysis. 242 91

The effect of pertussis toxin on somatostatin-induced K+ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K+ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma 1, 0/10 in adenoma 2). Spontaneous action potentials, K+, Na+, and Ca2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [32P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.
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PMID:Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells. 244 Mar 14

1. Intracellular recordings were made from neurones in the submucous plexus of the guinea-pig caecum and ileum. 2. Somatostatin hyperpolarized more than 90% of the neurones. The lowest effective concentration was 300 pM and the maximum hyperpolarization (about 30-35 mV) was caused by 30 nM. Under voltage clamp at -60 mV, somatostatin caused outward currents which reached a maximum of 350-700 pA. 3. The hyperpolarization or outward current reversed polarity at a membrane potential (about -90 mV in control solutions) which changed according to the logarithm of the external potassium concentration. 4. The somatostatin current showed inward rectification; when the inward rectification of the resting membrane was prevented by extracellular caesium or rubidium, the inward rectification of the somatostatin current also disappeared. 5. A potassium conductance with the same properties was increased by alpha 2-adrenoceptor agonists and by delta-opioid receptor agonists; however, the effects of somatostatin were unaffected by antagonists at alpha 2- or delta-receptors. The somatostatin analogue, cyclo-aminoheptanoyl-Phe-D-Trp-Lys-(benzyl)Thr, also did not antagonize the actions of somatostatin. 6. The hyperpolarization (or outward current) was unaffected by forskolin, cholera toxin, sodium fluoride, phorbol esters or intracellular application of adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S). However, when the recording electrode contained guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) the hyperpolarizations reversed only partially when somatostatin application was discontinued, and repeated applications caused the membrane potential to approach and remain close to the potassium equilibrium potential. 7. It is concluded that somatostatin increases the conductance of a set of inwardly rectifying potassium channels in submucous plexus neurones. The coupling between somatostatin receptor and ion channel involves a guanosine 5'-triphosphate-binding protein, but is not likely to result from changes in intracellular levels of cyclic adenosine 3',5'-monophosphate.
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PMID:Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurones. 245 Sep 94


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