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 receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred tumors. SS-R were found in most neuroendocrine tumors, i.e. GH and TSH producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R were also expressed in a majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R are rather differentiated (i.e. astrocytomas vs glioblastomas), but exceptions exist (high grade malignant lymphomas). An inverse relationship exists between SS-R and receptors for epidermal growth factor (EGF-R) incidence in lung tumors, glial tumors and most breast tumors, whereas meningiomas express simultaneously both receptors. A minority of tumors (ovarian tumors, MTC, insulinomas) express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function mediated by SS-R in human tumors may differ according to the tumor type. SS-R in pituitary and GEP tumor mediate hormone secretion inhibition with, in addition, possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Whereas SS-R seem to mediate antiproliferative effects in animal models and cell lines of lymphomas, breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors. The clinical implications of the presence of SS-R in tumors are manyfold: (1) as a predictive marker for efficient therapy with octreotide in pituitary and GEP tumors; (2) as a diagnostic marker: for pathobiochemical classification of tumors, using in vitro detection methods; for clinical evaluation using in vivo scanning techniques; (3) as a prognostic marker; and (4) as a potential radiotherapeutic target.
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PMID:Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. 135 16

The sulfonylurea glibenclamide, which is known to block ATP-sensitive potassium channels, increases, in a dose-dependent manner, the release of PRL from MMQ pituitary cells. Glibenclamide does not reduce the dopaminergic inhibition of forskolin-stimulated PRL secretion; conversely it almost completely abolishes the inhibitory effect of somatostatin (SRIF) on this parameter. The sulfonylurea dose dependently increases basal [Ca++]i, without affecting the increase in [Ca++]i induced by high concentrations of extracellular potassium. Glibenclamide does not modify dopamine-induced [Ca++]i reduction, whereas it abolishes the inhibitory effect of SRIF on basal [Ca++]i. In the presence of diazoxide, an opener of ATP-sensitive potassium channels, which lowers basal [Ca++]i, dopamine still reduces [Ca++]i whereas SRIF does not induce a further decrease. Glibenclamide induces the depolarization of the cell membrane and prevents the SRIF-evoked hyperpolarization. The hyperpolarization of the cell membrane induced by dopamine is not modified by glibenclamide. Diazoxide induces a cell membrane hyperpolarization that is enhanced by dopamine but not by SRIF. Finally, glibenclamide does not affect basal and stimulated adenylate cyclase activity. In conclusion, our findings show that, in MMQ cells, glibenclamide stimulates PRL release, suggesting an involvement of ATP-sensitive potassium channels in the regulation of PRL secretion. The reversal by glibenclamide of the effects of SRIF on calcium homeostasis, membrane potential, and PRL release suggests that this type of potassium channel participates to the somatostatinergic inhibition of PRL secretion. Conversely, we found that glibenclamide does not modify the dopaminergic inhibition of PRL secretion and second messenger systems, suggesting that ATP-sensitive potassium channels may not be involved in the inhibitory effect of dopamine on PRL release.
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PMID:Dopamine and somatostatin inhibition of prolactin secretion from MMQ pituitary cells: role of adenosine triphosphate-sensitive potassium channels. 135 54

Since there are conflicting reports regarding the effects of somatostatin (SS) on cyclic AMP levels in astrocytes derived from rat cerebral cortex and, to date, the SS binding to mature astrocytes is unknown, the present study has determined SS binding and its effect on cyclic AMP accumulation in a fresh astrocyte-rich suspension from rat cerebral cortex. 125I-Tyr11-SS binding was inhibited by SS in a dose-dependent manner. The Scatchard analysis of binding data was linear and yielded a dissociation constant of 0.95 +/- 0.15 nM with a maximal binding capacity of 122 +/- 13 fmol/mg protein. Vasoactive intestinal peptide (VIP) stimulated cyclic AMP accumulation up to 2.3 times above the basal levels whereas SS had no effect. This effect at any of the VIP concentrations. Likewise, SS did not inhibit the stimulation of cyclic AMP accumulation provoked by other effectors such as isoproterenol and forskolin. In view of our results and those of other authors, SS receptor localized in astrocytes must be able to couple with signal transduction systems other than adenylate cyclase, in order to carry out its biological actions in the cell.
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PMID:Somatostatin binding to a fresh rat astrocyte-enriched suspension. 135 80

Thyroid stimulating hormone (TSH) and other substances increase adenylate cyclase (AC) activity and growth of normal and neoplastic thyroid tissue. Factors that inhibit cAMP may provide targeted therapy to tumors dependent on cAMP for growth. Somatostatin has been reported to inhibit the growth of gastrinomas and carcinoid tumors. We therefore studied the effects of somatostatin on basal, TSH, pertussis toxin, and forskolin stimulated adenylate cyclase activity in normal and neoplastic thyroid tissue from 19 patients. Adenylate cyclase (AC) activity was determined by the conversion of alpha 32P-ATP to 32P-cAMP in pmoles/mg protein/30 minutes in an 8000 x g particulate fraction rich in thyroid plasma membranes. TSH (300 mU/ml) and forskolin (100 mM) (a diterpine that directly stimulates the catalytic unit of AC) increased AC activity in normal and neoplastic thyroid tissue. The AC stimulation was greater in the neoplasms (p less than 0.01). Somatostatin (5 x 10(-6)M) decreased basal and TSH stimulated AC activity below basal levels in both normal and neoplastic thyroid tissue (including papillary, follicular, and medullary carcinomas). The inhibition of AC by somatostatin was greater in neoplastic tissue (p less than 0.025). Pertussis toxin (which blocks the inhibitory guanyl nucleotide regulatory protein) was able to partially reverse the effect of somatostatin. Somatostatin partially inhibited forskolin stimulated AC activity. Somatostatin inhibits basal and TSH stimulated AC activity in both normal and neoplastic human thyroid tissue, with a greater effect on neoplasms. These studies establish that somatostatin blocks a major regulator of thyroid growth and provides the rationale for the use of somatostatin analogs in the treatment of thyroid cancers.
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PMID:Effect of somatostatin on adenylate cyclase activity in normal and neoplastic thyroid tissue. 135 26

Increasing evidence suggests that ethanol-induced changes in cyclic AMP (cAMP) signal transduction play a critical role in the acute and chronic effects of ethanol. Here we have investigated the effects of ethanol on cAMP signal transduction in primary cultures of rat hepatocytes. Acute exposure to ethanol had a biphasic effect on glucagon-receptor-dependent cAMP production in intact cells: 25-50 mM-ethanol decreased cAMP, whereas treatment with 100-200 mM-ethanol increased cAMP. After chronic exposure to 50-200 mM-ethanol for 48 h in culture, glucagon-receptor-dependent cAMP levels were increased, but no change in glucagon receptor number was observed. These effects of ethanol were independent of ethanol oxidation. Chronic ethanol treatment also increased adenosine-receptor- and forskolin-stimulated cAMP production. Increased cAMP production was also observed upon stimulation of adenylate cyclase with glucagon, forskolin and F- in membranes isolated from cells cultured with 100 mM-ethanol for 48 h. However, no differences were observed in basal and MnCl2-stimulated adenylate cyclase activity. The quantity of alpha i protein was decreased by 35% after chronic ethanol treatment, but no change in the quantity of alpha s protein was detected. Decreased alpha i protein was associated with a decrease in G(i) function, as assessed by the ability of 0.1 nM-guanosine 5'-[beta gamma-imido]triphosphate and 1 microM-somatostatin to inhibit forskolin-stimulated adenylate cyclase activity. Taken together, these results suggest that chronic exposure to ethanol increases receptor-dependent cAMP production in hepatocytes by decreasing the quantity of alpha i protein at the plasma membrane and thereby decreasing the inhibitory effects of G(i) on adenylate cyclase activity.
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PMID:Ethanol increases receptor-dependent cyclic AMP production in cultured hepatocytes by decreasing G(i)-mediated inhibition. 135 61

We employed a cyclic AMP-resistant subclone of UMR 106-01 osteoblastic osteosarcoma cells (UMR 4-7) with a regulated, dominant-negative mutation of cyclic AMP-dependent protein kinase (PK-A), to examine the mechanism(s) whereby parathyroid hormone (PTH) regulates growth of these cells. Expression of a transiently transfected CAT reporter gene controlled by the cAMP response element of the rat somatostatin gene ('SST-CAT') was used to monitor PK-A activation in intact cells. Agonist-stimulated SST-CAT expression was specific for agents known to activate adenylate cyclase, required an intact cAMP response element and was specifically blocked following induction of the mutant cAMP-resistant phenotype in UMR 4-7 cells. Inhibition of the proliferation of UMR 106-01 cells by PTH, which is mimicked by forskolin and 8-bromo-cAMP, was blocked completely in mutant cyclic AMP-resistant UMR 4-7 cells. We conclude that control of proliferation in UMR 106-01 cells by PTH involves the cAMP messenger system and requires activation of PK-A.
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PMID:Regulation of gene transcription and proliferation by parathyroid hormone is blocked in mutant osteoblastic cells resistant to cyclic AMP. 135 85

The secretion of growth hormone (GH) is controlled by a complex regulatory system. The primary control is exerted by two neuroendocrine hormones, GH-releasing hormone and somatostatin, though other hypothalamic neuropeptides directly and indirectly participate in this process. The regulation of each of these neurohormones is now being clarified at both physiologic and molecular levels, as are their respective roles in the generation of pulsatile GH secretion and in GH feedback regulation. Considerable information has been amassed concerning signal transduction systems mediating the effects of hypothalamic hormones on GH secretion. Although multiple second messengers have been implicated, the adenylate cyclase-cyclic AMP-protein kinase A system appears to exert a predominant role. The developmental regulation of the somatotropes and of GH gene expression is also of importance in determining the GH responses to releasing and inhibiting hormones. The availability of several rodent strains with genetic disorders of growth associated with impaired GH secretion, along with the development of transgenic models, has permitted a more detailed analysis of the role of cytokines and growth factors on both somatotrope biology and hormone secretion. Finally, knowledge gained from studies in animals is permitting a better understanding of the mechanisms involved in physiologic GH secretion and altered GH secretion associated with specific disease states in humans.
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PMID:Regulation of growth hormone secretion. 136 Sep 11

Somatostatin (SS) receptors in membranes from ovine retinas were examined using 125I-Tyr11-SS as a ligand. Receptor binding was rapid, specific, saturable, reversible and dependent on temperature and membrane concentration. Conditions of apparent equilibrium were obtained at 25 degrees C after a 45 min incubation in the presence of about 0.25 mg membrane protein/ml. Native SS competitively inhibited the binding of 125I-Tyr11-SS in the range of 0.01-10 nM, and half-maximal inhibition was observed at 0.2 nM SS. Scatchard analysis of these data suggested the existence of a single population of SS receptors with a dissociation constant of 0.23 +/- 0.03 nM and a maximum binding capacity of 84 +/- 6 fmol/mg protein. The binding of 125I-Tyr11-SS was inhibited by various synthetic SS analogs in a dose-dependent manner whereas peptides unrelated to SS did not show practically any effect even at concentrations as high as 10(-6) M. SS receptor occupancy appears to be coupled to inhibition of adenylate cyclase activity by a guanine nucleotide-binding regulatory protein, as suggested by the facts that: (a) SS noncompetitively inhibited the stimulatory effect of vasoactive intestinal peptide (VIP) (3 x 10(-7) M) on membrane adenylate cyclase activity but it did not alter basal enzyme activity; and (b) the addition of guanosine 5'-triphosphate (GTP) (10(-5) M) decreased the specific binding of 125I-Tyr11-SS to 26.6% of the control value due to a decrease in SS receptor affinity. The present results support the hypothesis that SS may contribute to the physiological regulation of the functions of the retina.
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PMID:Somatostatin binding and modulation of adenylate cyclase in ovine retina membranes. 136 Sep 27

Patients with medically intractable temporal lobe epilepsy (TLE) undergo medial temporal lobectomy with hippocampectomy for one of two reasons. (1) A lesion (tumor or arteriovenous malformation) adjacent to, but not invasive of, the hippocampus, results in the removal of the lesion and adjacent hippocampus in order to ensure a tumor-free margin. This group will be referred to as tumor-related TLE (TTLE) patients. (2) The operation is performed when depth electrode recordings and other evaluative techniques point to the hippocampus as the focus of seizure initiation. This group will be referred to as cryptogenic TLE (CTLE) patients. Analysis of the hippocampi of these two groups of patients reveals that the TTLE hippocampus is quite similar to that of autopsy subjects in its chemical neuroanatomy. However, the dentate gyrus of the CTLE patients shows considerable morphological and cytochemical reorganization. This reorganization is characterized by a number of features. (1) There is a loss of granule cells which occurs either as a patchy loss and/or a thinning of the granule cell layer. (2) Remaining granule cells which contain dynorphin appear to produce recurrent collaterals into the inner molecular layer of the dentate gyrus. (3) In the subgranular region of the hilus (the polymorphic layer) there is a selective loss of interneurons immunoreactive for somatostatin, neuropeptide Y and substance P. (4) There appears to be an increase in fibers immunoreactive for somatostatin and neuropeptide Y which extend throughout the dentate molecular layer. Somatostatin fibers being less numerous than neuropeptide Y fibers (5). The distributions of a number of neurotransmitter receptors also show striking reorganization in the dentate gyrus of the CTLE hippocampus. (6) Second messenger systems protein kinase C and adenylate cyclase, and Na+, K(+)-ATPase activity, as determined by ouabain binding, is increased in the molecular layer of CTLE. This remodeling of the CTLE hippocampus may hold the key to the mechanisms of hyperexcitability of the granule cells in the hippocampus of this group, and consequently the generation of seizures. The removal of the hippocampus in CTLE patients results in good control of seizures, whereas removal of hippocampi that do not show such reorganization, in a group of patients classified as atypical CTLE patients, results in inadequate seizure control. These findings suggest a complex series of processes in converting the properly regulated granule cells into hyperexcitable ones.
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PMID:Neurotransmitters and their receptors in human temporal lobe epilepsy. 136 31

This study demonstrates the dual regulation by somatostatin of vasoactive intestinal peptide (VIP)-stimulated and forskolin-stimulated cyclic AMP accumulation by isolated rat intestinal epithelial cells. Somatostatin non-competitively inhibited (IC50 = 1 microM) the stimulatory effect of VIP on cyclic AMP accumulation, suggesting that the two neuropeptides act through separate receptors. The cyclic AMP accumulation produced by forskolin (a diterpene that stimulates directly the catalytic subunit of adenylate cyclase) was also inhibited by somatostatin in a dose-dependent manner. However, somatostatin did not modify the stimulatory effect of VIP on adenylate cyclase activity in a membrane preparation from the same cells, making it difficult to explain the mechanism of somatostatin action at this level. The data presented here suggest that somatostatin may play a physiological role in the regulation of nutrient absorption and the release of gut hormones or exocrine secretions by intestinal epithelial cells through the modulation of cyclic AMP production.
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PMID:Somatostatin inhibits VIP- and forskolin-stimulated cyclic AMP accumulation in enterocytes from rat jejunum. 136 40


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