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)

Sixteen post-menopausal patients with advanced breast cancer were treated with a long acting somatostatin analogue, SMS 201-995 (Sandostatin): 0.1 mg bid sub-cutaneously. The dose was chosen on the basis of efficiency in acromegaly treatment. SMS 201-995 activity was evaluated assaying Insulin Growth Factor 1 (IGF1) plasma concentration. A merely partial IGF1 decrease was noted. To be evaluable for response, patients had to be treated for at least 30 days. Among the 14 evaluable patients, we observed no response to SMS 201-995. However, we noted tumor stabilization in 3 patients after a 90 days treatment period. Side-effects were very mild. This first report on SMS 201-995 treatment of breast cancer suggests that further studies evaluating the effect of other modes of administration or drug association should be warranted.
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PMID:Effect of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) in advanced breast cancer. 253 68

This paper reports the phenomenon of dependence to a somatostatin octapeptide analog used for the treatment of acromegaly and severe headache. The mechanism of this dependence is still unknown, but could be based on the interaction of the somatostatin analog with opioid receptors. Analgesia may be at least partially supported by the opioid modulation of pain transmission, but also by general "appetitive" behavioral activation due to the effect of somatostatin on its receptors.
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PMID:The development of dependence to an octapeptide somatostatin analog: contribution to the study of somatostatin analgesia. 254 10

The correlation between response of plasma GH to GHRH and the GHRH-induced stimulation of the intracellular adenylate cyclase (AC) activity in pituitary adenoma cell membranes in acromegalic patients was investigated. Each peak plasma GH level after iv administration of GHRH ranged from 1.1 to 13.8 times the basal level in 13 acromegalic patients. On the other hand, the maximal stimulation of intracellular AC activity (cAMP production) induced by GHRH varied from 1.4 to 6.4 times the control level in each GH-producing pituitary adenoma cell membrane. A significant positive correlation (r = 0.89, P less than 0.005) between plasma GH response to GHRH and intracellular cAMP production stimulated by GHRH was observed in nine of the acromegalic patients. In contrast, the response of plasma GH to GHRH was significantly blunted, despite a fairly large production of intracellular cAMP stimulated by GHRH, in the other four acromegalic patients. These results suggest that GHRH-induced GH release from GH-producing pituitary adenomas of patients with acromegaly may be regulated not only by GHRH receptor-adenylate cyclase system but also modified by several other factors including somatostatin and Sm-C.
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PMID:Growth hormone releasing hormone-sensitive adenylate cyclase activity in growth hormone-producing pituitary adenoma: correlation to the response of plasma growth hormone to growth hormone releasing hormone in patients with acromegaly. 255 Feb 7

Octreotide is a long-acting cyclic octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin. It can suppress the secretion of serotonin, as well as the gastroenteropancreatic peptides gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, and pancreatic polypeptide. It also suppresses growth hormone and decreases splanchnic blood flow. Octreotide is completely and rapidly absorbed following subcutaneous injection and has an elimination half-life of 1.5 hours. Clinical trials reviewed here show octreotide useful in the treatment of diarrhea associated with VIP secreting tumors, as well as diarrhea and flushing associated with carcinoid syndrome, both conditions for which the drug is approved. Clinical trials involving the use of octreotide in the treatment of acromegaly are also reviewed. Adverse reactions to octreotide are mild to moderate and most commonly involve injection site pain and diarrhea. Drug interactions are apparently related to the drug's pharmacologic effects. Octreotide is given subcutaneously two to three times daily, with daily doses ranging from 50mcg to 1,500mcg per day. Further research appears necessary to clarify dosing issues.
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PMID:Debut of a somatostatin analog: octreotide in review. 255 39

Somatostatin (SRIF) actions in the brain and pituitary are mediated by specific receptors. Using radioiodinated ligands it has been possible to characterize the kinetics of specific binding sites in the brain and pituitary, and to determine their cellular localization by autoradiography. At the pituitary level, the inhibition of growth hormone, prolactin and thyrotropin secretions induced by SRIF is mediated through a single binding site which is coupled to the inhibition of adenylate cyclase. In the brain, SRIF receptors are localized on neurons and glial cells and are also coupled to adenylate cyclase inhibition. Two sites are differentiated in the brain with an analogue of somatostatin, SMS 201995. In humans, SRIF-binding sites have been related to a number of pathologies. At the pituitary level, it has been shown that the number of binding sites was negatively correlated to growth hormone levels in acromegaly. Furthermore, SRIF-binding sites were undetectable in a patient which did not respond to SMS 201995 therapy. In the brain, meningiomas and gliomas are rich in SRIF binding sites. This suggests a possible role for SRIF on glia. In neurodegenerative diseases, cortical SRIF concentrations are decreased in Alzheimer's and Parkinson's disease associated with dementia while SRIF-binding sites are only affected in Alzheimer's disease. In conclusion, the physiological role of SRIF in the brain and pituitary can be evaluated by studying the receptors of the peptide. Such studies allow to question the implication of SRIF in endocrine and neuropathologies.
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PMID:Somatostatin receptors in brain and pituitary. 256 73

GH secretion in acromegaly was studied in 8 patients before and during treatment with SMS 201-995, a somatostatin analogue, 100 micrograms twice daily, by evaluating GH day profiles and GH suppressibility after oral glucose tolerance tests (OGTT). Normalization of GH secretion, estimated by OGTT, was only observed in the three patients who had a decrease in plasma GH to less than 2 micrograms/l after SMS 201-995 injection, and who had the lowest mean plasma GH levels during the day and the largest percent decline of mean plasma GH levels. We conclude that real normalization of GH secretion during SMS 201-995 therapy only occurs in a subset of patients. The data illustrate that the applicability of the generally held cut-off value of 5 micrograms/l, between normal and abnormal plasma GH, has to be reconsidered in the case of chronic intermittent subcutaneous therapy with SMS 201-995.
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PMID:Does SMS 201-995 normalize growth hormone secretion in acromegaly? GH day profiles and GH concentrations after oral glucose loading. 259 40

A 60-year-old woman with acromegaly associated with sleep apnea was treated with the somatostatin analogue SMS 201-995 (Sandoz) for several months. Growth hormone levels were normalized and a rapid improvement in sleep apnea was controlled with polygraphic nocturnal monitoring. Hypophysectomy seems to have variable effects on sleep apnea in acromegaly. The origin of obstructive apnea in acromegaly is therefore unclear.
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PMID:[Long-term effects of treatment with SMS 201-995 on sleep apnea syndrome associated with acromegaly]. 261 48

To determine whether human calcitonin inhibits GH secretion in acromegaly, as previously described for healthy subjects, the effect of an i.v. bolus injection of calcitonin or saline on GH levels in patients with active acromegaly was studied and compared to that of an i.v. bolus injection of the synthetic somatostatin analogue, octreotide. After the injection of calcitonin, GH levels decreased by 46% of initial values, whereas octreotide reduced GH levels by 87% and saline had no significant effect. Administration of calcitonin to acromegalics did not cause the transient rise in plasma PRL and TSH levels seen in normal subjects. Octreotide induced a decrease in plasma PRL in three out of seven patients. It is concluded that human calcitonin suppresses GH secretion in acromegaly, but not to normal levels; moreover the effect is less than that found for octreotide. In addition, acromegalic patients did not exhibit the PRL and TSH-releasing activity of calcitonin found in normal subjects, while octreotide inhibited PRL secretion in some acromegalic patients.
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PMID:The effect of calcitonin on growth hormone secretion in acromegaly. 262 52

There have now been many studies on the effects of growth hormone (GH) on renal function. Chronically elevated GH levels, such as occur in acromegaly, are associated with an increase in renal plasma flow (RPF), glomerular filtration rate (GFR) and kidney size. When GH falls in these individuals (such as, after hypophysectomy in acromegalic patients), RPF, GFR and renal size decrease. A rapid increase in plasma GH in normal or growth hormone deficient adults, such as occurs after GH injection, causes an increase in RPF and GFR. However, these effects on renal function are delayed, occurring between 5.5 and 23 hours after the GH injection and in association with an elevation in the plasma concentrations of insulin-like growth factor I (IGF-I). These observations suggest that IGF-I may mediate the GH stimulated increase in RPF and GFR. We evaluated this question in rats starved for three days. A 20 minute infusion of IGF-I causes an increase in RPF and GFR in these animals. This effect could be blocked by indomethacin but not by somatostatin. These findings suggest that: 1) GH injection does increase RPF and GFR; 2) this effect on GH, which is delayed for several hours seems to be mediated by IGF-I; and 3) a 20-minute IGF-I infusion itself increases RPF and GFR in starved rats. The effect of IGF-I on renal function seems to require the presence of eicosanoids. Further studies will be necessary to examine whether IGF-I is a physiological regulator of renal function.
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PMID:Effects of growth hormone and IGF-I on renal function. 263 57

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects and drug interactions, dosage, availability and cost, and indications for use of octreotide, a new synthetic analogue of the peptide hormone somatostatin (SS), are reviewed. Like SS, octreotide suppresses secretion of pituitary growth hormone (GH) and thyrotropin and decreases release of a variety of pancreatic islet cell hormones including insulin, glucagon, and vasoactive intestinal peptide (VIP). Octreotide also reduces splanchnic blood flow, gastric acid secretion, GI motility, and pancreatic exocrine function and alters the absorption of water, electrolytes, and nutrients from the GI tract. The elimination half-life of i.v. octreotide is 72-98 minutes, compared with 2-3 minutes for i.v. SS. Usual administration of octreotide is by the i.v. or s.c. route. Octreotide has been studied in the treatment of hormone-secreting pituitary tumors and pancreatic islet cell tumors. Octreotide therapy lowers GH secretion and improves clinical symptoms in patients with acromegaly and may suppress clinical symptoms to a greater degree than bromocriptine. Patients with carcinoid syndrome and VIP-secreting tumors (vipomas) have had substantial improvement in clinical symptoms with administration of octreotide. This agent does not appear to be effective in the treatment of nonvariceal upper GI bleeding and acute pancreatitis; its relative usefulness in the treatment of variceal bleeding is not established. Adverse effects associated with octreotide therapy generally have been mild, including pain or burning at the injection site, abdominal pain, and diarrhea. Octreotide has been shown to interfere with absorption of oral cyclosporine. Standard initial therapy is octreotide acetate 50-100 micrograms s.c. every 8-12 hours, with titration based on clinical and biochemical effects. Up to 3000 micrograms/day of octreotide acetate has been administered to patients with acromegaly without serious adverse effect. Octreotide is marketed under the brand name Sandostatin and is available in 1-mL ampuls containing 50, 100, and 500 micrograms of octreotide acetate. Because the conditions for which octreotide appears to be most effective are uncommon, the drug should be considered for addition to the formulary in tertiary-care institutions only; addition of octreotide to the formulary of a community hospital is probably unnecessary. The synthetic analogue octreotide is longer acting and more specific in pharmacologic action than SS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Octreotide, a new somatostatin analogue. 265 11


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