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)

This study was undertaken to determine whether intermittent pancreatic juice diversion (PJD) from the intestine can induce pancreatic and duodenal growth. Concomitant infusions of SMS 201-995, a somatostatin analog, and L-364,718, a cholecystokinin (CCK) receptor antagonist, were used to establish the involvement of endogenous CCK. Fed rats equipped with biliary, duodenal, and pancreatic cannulae had their pancreatic juice diverted 8 h/day for 4 days and were infused or not with either SMS 201-995 (5 micrograms/kg.h) or L-364,718 (0.5 mg/kg.h) during diversion. After 4 days, rats were killed, and their pancreas and duodenum were excised for measurements of parameters indicative of growth. In normally fed rats with pancreatic juice returned, SMS 201-995 inhibited daily pancreatic secretions of volume and protein, whereas L-364,718 inhibited only protein output. These two inhibitors had no effect on normal pancreatic and duodenal growth. PJD was associated with increased volume and protein output, increased plasma CCK level, and pancreatic growth. All of these effects were completely blocked by SMS 201-995 and L-364,718, with the exception of plasma CCK level by the CCK antagonist. None of these treatments affected duodenal growth. These results suggest that intermittent infusions of these two inhibitors had no effect on normal pancreatic and duodenal growth, but were successful in preventing pancreatic growth induced by PJD. They also indicate that endogenous CCK is involved in PJD-induced pancreatic growth.
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PMID:Endogenous cholecystokinin release responsible for pancreatic growth observed after pancreatic juice diversion. 195 73

Neuropeptides are common mediators of the nervous and the immune systems. We investigated whether two families of peptides, calcitonin (CT) and somatostatin, posses human monocyte chemotactic activity. CT-related peptides induce a significant chemotactic response, and the potency order is: salmon CT greater than human CT greater than CT much greater than carbo-CT; CT gene-related peptide is completely inactive. This rank potency order differs from that in other systems (e.g. bone and nervous system). The chemotactic response of monocytes obtained from patients chronically treated with either salmon CT or carbo-CT is impaired, thus suggesting a phenomenon of down-regulation of a common receptor on monocytes. While somatostatin-(1-14) is completely inactive on monocyte chemotaxis, the synthetic analog SMS 201995 is extremely potent. Also, in this case the prolonged treatment of patients with SMS 201995 leads to an impaired chemotactic response.
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PMID:Human monocyte chemotactic activity of calcitonin and somatostatin related peptides: modulation by chronic peptide treatment. 196 76

Somatostatin receptors were solubilized from rat pancreatic membranes with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonic acid (CHAPS). The binding of an iodinated somatostatin analog [125I-Tyr3]SMS to the soluble fraction was time-dependent, saturable, and reversible. Scatchard analysis of equilibrium binding data indicated that the soluble extract contained a single class of somatostatin binding sites with a Kd of 0.3 nM and a Bmax of 210 fmol/mg. As observed with membrane-bound receptors, soluble binding receptors were sensitive to the GTP analog GTP gamma S indicating that they are functionally linked to a G protein. A molecular weight of about 400,000 was determined for soluble receptors under native conditions by gel filtration. In denaturing gel electrophoresis, photoaffinity labeling of soluble receptors identified a major protein of Mr = 100,000 and two minor proteins of Mr = 56,000 and 21,000. Isoelectric focusing of soluble receptors revealed that the somatostatin receptor is an acidic protein with pI 4.8. The soluble somatostatin receptor is a glycoprotein which can be specifically bound to the wheat germ agglutinin lectin and eluted by triacetyl-chitotriose.
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PMID:Solubilization and characterization of active somatostatin receptors from rat pancreas. 196 49

We have studied the glucose response and catecholamine (CA) response to insulin in the conscious rat to evaluate the role of sensory fibers in these responses in animals pretreated with capsaicin as neonates. In contrast to previous results obtained in anesthetized rats (Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 370: 201-215, 1986; Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 391: 511-526, 1987.), in conscious rats, insulin (1 IU/kg iv) produced only a mild hypoglycemia, which quickly returned to resting levels and caused no significant changes in plasma epinephrine levels. Somatostatin and SMS-(201-995), a somatostatin analogue, both potentiated and prolonged the insulin-induced hypoglycemia, resulting in an increase in circulating CA levels that was suppressed by hexamethonium and atropine. In capsaicin-pretreated rats the blood glucose levels at 90 min after insulin were significantly lower than those in vehicle-pretreated rats both in the presence (1 IU/kg insulin, 48 +/- 6 vs. 92 +/- 6 mg/100 ml, P less than 0.01) and absence (10 IU/kg insulin, 38 +/- 4 vs. 51 +/- 2 mg/100 ml, P less than 0.01) of SMS-(201-995). The CA levels in capsaicin-pretreated rats at 90 min after insulin were higher than in vehicle-pretreated rats (epinephrine levels: 27 +/- 4 vs. 10 +/- 1 pmol/ml in 1 IU/kg insulin, P less than 0.01; 64 +/- 14 vs. 25 +/- 5 pmol/ml in 10 IU/kg insulin, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Capsaicin-sensitive nerves are required for glucostasis but not for catecholamine output during hypoglycemia in rats. 196 8

Somatostatin (somatotropin release inhibiting factor; SRIF) has widespread functions as a modulator of neural activity as well as of endocrine and exocrine secretion. In the present paper, the binding characteristics of somatostatin receptors have been investigated in rat long bones using the stable analogue, 125I-SDZ 204-090, as a ligand. Binding studies revealed the presence of a single class of high-affinity binding sites for 125I-SDZ 204-090 on cells prepared from neonatal rat long bones with an equilibrium dissociation constant (KD) of 70.1 +/- 8.2 pM (n = 3). An excellent correlation was found between the ability of various somatostatin analogues to inhibit growth hormone in pituitary cells and to displace the binding of 125I-SDZ 204-090 to the bone cell preparation, indicating that the receptors are very similar, if not identical. The localization of the somatostatin-binding sites was examined by autoradiography after labelling in vitro and in vivo. The binding sites were shown by both procedures to be selectively localized to the metaphysis of rat long bones. The labelling experiments in vivo indicate that these receptors can be reached in the living animal by circulating somatostatin analogues. In addition, the analogue SMS 201-995 inhibited the forskolin-stimulated adenylate cyclase activity in bone cell suspensions. These results suggest that somatostatin could be an important regulatory factor in bone metabolism.
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PMID:Identification and characterization of somatostatin receptors in neonatal rat long bones. 196 33

The binding characteristics of several somatostatin (SS-14) analogs developed in our laboratory were examined in various human and animal tumors and normal tissues. In rat cerebral cortex and human breast cancer membranes the interaction of SS-14 with its binding sites was rapid, specific, saturable, linear with protein concentrations, and dependent on time and temperature. Analysis of kinetic and equilibrium experimental data showed that the interaction of [125I-Tyr11]SS-14 with the binding sites in all normal and tumoral tissue specimens was consistent with the presence of a single class of noncooperative binding sites. Superactive octapeptide analogs of somatostatin-containing hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys showed significant binding affinities to SS-14 receptors. Among these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I) showed the highest binding affinity to normal human pancreatic tissue and human pancreatic adenocarcinoma. In contrast, Sandostatin (SMS 201-995) bound only to normal pancreas, not to human pancreatic cancers. Analog RC-98-I also showed a high binding to human and rat prostate cancers. In human epithelial ovarian cancers and an arrhenoblastoma, analogs D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2 (RC-95-I), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) appeared to be the most potent in displacing labeled SS-14. Analogs Ac-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-101-I) as well as RC-121, RC-160, and RC-95-I, but not SMS-201-995, showed high binding affinity in human breast cancers. In specimens of human meningioma the highest binding was found with analogs RC-121, RC-95-I, and RC-101-I. Since marked variations in binding affinities were noted for several analogs in the tissues of origin and the tumors, this suggest that differences may exist between somatostatin receptors not only in normal vs. cancerous tissues, but also among various tumors. Our findings also imply that some analogs could be therapeutically superior to others in the treatment of certain tumors.
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PMID:Evaluation of receptors for somatostatin in various tumors using different analogs. 196 67

We determined islet amyloid polypeptide (IAPP) response in plasma to oral and intravenous glucose administration and intravenous insulin injection in nondiabetic subjects. Moreover, we studied the effect of somatostatin analogue SMS 201-995 on glucose-induced IAPP secretion in nondiabetic subjects. Plasma IAPP concentration was determined by radioimmunoassay. Oral administration of 75 g glucose (n = 8) significantly increased plasma IAPP levels from 4.5 +/- 0.7 to 14.0 +/- 1.7 pM (P less than 0.01) 60 min after administration. Intravenous administration of 10 g glucose (n = 7) also caused a significant increase in plasma IAPP from 5.0 +/- 0.4 to 11.6 +/- 0.9 pM (P less than 0.01) 5 min after injection. Plasma IAPP significantly decreased from 5.1 +/- 0.4 to 2.9 +/- 0.4 pM (P less than 0.01) 60 min after intravenous insulin injection (n = 8). Pretreatment with SMS 201-995 completely abolished IAPP and insulin secretion to intravenous glucose injection. A significant correlation was found between plasma IAPP and insulin levels in oral and intravenous glucose administration and between plasma IAPP and C-peptide levels during insulin-induced hypoglycemia. These results suggest that IAPP is cosecreted with insulin in response to a glucose load and secretion of IAPP is inhibited by hypoglycemia and somatostatin. IAPP may serve as a novel pancreatic hormone to control carbohydrate metabolism.
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PMID:Islet amyloid polypeptide response to glucose, insulin, and somatostatin analogue administration. 197 May 40

It has previously been reported that a somatostatin analogue has a direct antiproliferative effect on human breast cancer cells in vitro. Here we report preliminary data on the effects of the in vivo administration of SMS in patients with advanced breast cancer. The regimen consisted of iv infusion of 750 micrograms SMS t.i.d. for 10 days followed by 5 days at 500 micrograms im b.i.d. A partial response was observed in 3 out of 10 patients treated. Moreover, a marked reduction of oedema, cyanosis and bleeding from ulcerated tumor lesions was noted in most of the treated patients. Administration of SMS was devoid of toxic side effects. It is suggested that SMS may be of potential value in the therapeutic approach to advanced breast cancer.
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PMID:Advanced breast cancer: response to somatostatin. 197 Jul 16

The interaction of adrenergic and peptide receptors linked to adenylate cyclase and the inhibition by bioactive peptides of stimulated cyclic AMP production has been investigated in intact, excised rabbit ciliary processes. Cyclic AMP production stimulated by isoproterenol, vasoactive intestinal peptide, or forskolin was inhibited by the biologically active peptides neuropeptide Y, somatostatin, and the synthetic somatostatin analogue SMS 201-995. IC50s determined from dose-response curves of inhibition are consistent with the known abilities of these ligands to modulate cyclic AMP and physiological responses in other tissues. Inhibition by neuropeptide Y or SMS 201-995 was unaffected by the specific alpha 2-adrenergic antagonist yohimbine, which shows that peptide inhibition is not occurring via peptide binding to the inhibitory alpha 2-adrenergic receptor. These results suggest that endogenous peptides may participate in modulation of cyclic AMP production and subsequent physiological events influenced by cyclic AMP levels in rabbit ciliary processes by inhibiting stimulated cyclic AMP synthesis.
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PMID:Neuropeptide Y and somatostatin inhibit stimulated cyclic AMP production in rabbit ciliary processes. 197 Dec 7

The aim of our study was to compare the effectiveness of bromocriptine vs. long acting somatostatin analogue (SMS 201-995) on growth hormone suppression in active acromegaly. A twenty year old female, student of law, was previously treated with Parlodel LA 50 mg i.m. injection and then with bromocriptine 30 mg orally for 2.5 years because of active acromegaly and very large intrasellar and suprasellar pituitary adenoma. She was partial bromocriptine responder with mean growth hormone levels prior the treatment 30 mU/L and after bromocriptine 13.7 mU/L and with gross tumor shrinkage. Since she failed to restore menstrual cycles, had clinical signs of the disease, she was taken off bromocriptine and treated with somatostatin analogue (SMS 201-995) 300 mcg s.c. daily and 400 mcg s.c. daily with mean growth hormone levels 10 mU/L. She was also treated with combined treatment (400 mcg s.c. SMS 201-995 plus 30 mg bromocriptine orally) and mean growth hormone levels were 11 mU/L. SMS 201-995 had a long lasting inhibitory effect on growth hormone secretion in acromegaly (p less than 0.01) but in comparison to daily growth hormone levels during bromocriptine treatment no difference was found (p greater than 0.01). Combined treatment with SMS 201-995 and bromocriptine did not achieve greater suppression of daily growth hormone levels than those achieved with SMS 201-995 alone (p greater than 0.1) or with bromocriptine alone (p greater than 0.05). No significant tumor shrinkage during chronic SMS treatment was seen. Severe clinical and biochemical signs of hypoglycaemia were registered on one occasion only during the first month of treatment with SMS 201-995.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison among the effectiveness of growth hormone suppression in active acromegaly of bromocriptine and long acting somatostatin analogue (SMS 201-995). 197 22


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