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 (SRIF) inhibits both basal and vasoactive intestinal peptide (VIP)-stimulated hormone secretion by the GH4C1 clonal strain of rat pituitary tumor cells. We have previously shown that SRIF inhibits cAMP accumulation stimulated by VIP but does not alter basal cAMP levels in this cell line. To determine the importance of changes in cAMP accumulation in the mechanism of SRIF action, we have compared the effect of SRIF on hormone release stimulated by VIP and two other secretagogues which increase effective intracellular cAMP concentrations: forskolin and 8-Bromo-cAMP (8-Br-cAMP). VIP stimulated GH and PRL secretion to the same maximal extent (220% of control) with similar ED50 values (0.37 +/- 0.03 and 0.43 +/- 0.08 nM, mean +/- SE, respectively). SRIF (100 nM) reduced maximal VIP-stimulation of both GH and PRL release from 220 to 140% of control; however, it did not significantly change the ED50 values for VIP. The effect of SRIF on VIP-stimulated hormone release parallels its action on VIP-stimulated cAMP accumulation. Furthermore, the concentrations of SRIF required to produce half-maximal inhibition of VIP-stimulated GH and PRL release (0.8 +/- 0.2 nM and 0.7 +/- 0.1 nM, respectively) were similar to its potency to inhibit VIP-stimulated cAMP accumulation (1.2 +/- 0.1 nM). These data indicate that changes in cAMP levels mediate inhibition of VIP-stimulated hormone secretion by SRIF. Forskolin increased cAMP accumulation with an ED50 value of 2.4 +/- 0.5 microM. A maximal concentration of forskolin (100 microM) stimulated cAMP accumulation to a greater extent than 100 nM VIP (34 +/- 4-fold vs. 9 +/- 1-fold). Together, forskolin (100 microM) and VIP (100 nM) stimulated cAMP accumulation by more than 50-fold. However, PRL secretion in response to maximal concentrations of VIP or forskolin individually or together were the same (approximately 200% of control). These results support the conclusion that both compounds stimulate PRL secretion by a cAMP-mediated mechanism which can be fully activated by either one alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Somatostatin inhibits basal and vasoactive intestinal peptide-stimulated hormone release by different mechanisms in GH pituitary cells. 613 45

The role of ACTH-(1-24) on angiotensin II receptors has been studied in bovine adrenal glomerulosa cells in primary culture. Angiotensin II receptors were measured in cells pretreated or not by ACTH-(1-24) on day 4 of culture. ACTH-(1-24) decreased angiotensin II binding sites in a time and a dose-dependent manner. After 24 hours of treatment the minimal effective dose of ACTH-(1-24) was 10(-11)M and the maximal effect was obtained with 10(-8)M. Moreover, ACTH-(1-24) 10(-8)M decreased significantly angiotensin II receptors after 6 hours of treatment. Scatchard plot analysis showed that ACTH-(1-24) treatment did not modify the affinity of angiotensin II receptors (Ka = 0.42 and 0.44 X 10(9)M-1 in control and treated cells respectively) but reduced by about half the number of angiotensin II sites per cell. Like ACTH-(1-24), 8-Bromo-cAMP, forskolin and cholera toxin decreased angiotensin II receptors. Factors such as prolactin, somatostatin, ACTH-(11-24) and dopamine which are bound to adrenal membranes without increasing cAMP production had no effect. In conclusion, these studies in vitro demonstrate for the first time that ACTH decreases angiotensin II receptors by a direct mechanism acting on glomerulosa cells, and they also suggest that this effect could be mediated by cAMP.
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PMID:Adrenocorticotropin regulates angiotensin II receptors in bovine adrenal cells in vitro. 632 3

Sera from patients with insulin-dependent diabetes mellitus (IDDM) containing islet cell surface antibodies (ICSA) were studied for their capacity to lyse cultured rat islet cells. The uptake of ethidium bromide was used to identify lysed cells and immunofluorescent staining with antisera to insulin, glucagon, somatostatin, or pancreatic polypeptide was used to identify the different islet cell types (B-, A-, D-, and PP-cells, respectively). Our experiments showed that in the presence of complement, sera containing ICSA lysed 81% of the B-cells, but 10% or less of the A-, D-, and PP-cells. Normal control sera resulted in lysis of less than 4% of each of the islet cell types. The demonstration that ICSA are preferentially lytic for B-cells may be important in defining the role of these autoantibodies in the pathogenesis of IDDM, particularly since the B-cell mass in diabetics is markedly reduced relative to the other islet cell types.
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PMID:Preferential lysis of pancreatic B-cells by islet cell surface antibodies. 675 62

Series of recombinant plasmids for expression of the synthetic gene somatostatin-14 (SST) as a fusion protein were obtained. The somatostatin gene was fused to chloramphenicol acetyltransferase (cat) or its deleted variant genes. Both parts of the resultant fusion protein were joined through a Met residue. The hybrid gene was expressed under the control of the cat gene promoter (Pcat), the tryptophan operon promoter (Ptrp) or the promoter of bacteriophage T5 (PT5). These fusions gave insoluble polypeptide products amounting from 5-10% of the total cellular protein under constitutive biosynthetic conditions (Pcat) to 5-30% upon induction (Ptrp, PT5). A correlation between the efficiency of expression and the length of cat, the power of the promoter used and the absence or presence of transcription terminators, was studied. The scheme for SST isolation from bacterial cells was developed. SST was liberated from the fused polypeptide by treatment with cyanogen bromide and purified to homogenity by a combination of chromatographic steps: gel filtration, ion-exchange and rpHPLC. The renaturated recombinant SST showed specific biological and immunological activities and had 98% purity. The yield was 1 mg of the purified cyclic SST/1 culture of E.coli.
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PMID:[Genetic engineering in the bacterial synthesis of somatostatin]. 774 53

1. Noradrenaline hyperpolarizes guinea-pig submucosal neurones by opening inwardly rectifying potassium channels. Intracellular recordings were made from submucosal neurones and the possible involvement of the phospholipase A2 pathway in this response was examined. 2. The non-specific phospholipase A2 inhibitors, quinacrine (10 microM) and 4-bromophenacyl bromide (4-BPB, 10 microM) inhibited nerve-evoked inhibitory synaptic potentials (i.p.s.ps) and hyperpolarizations to somatostatin and UK 14304. Quinacrine and 4-BPB also blocked the inward rectification present in current-voltage curves in the absence of somatostatin or UK 14304. 3. The more selective phospholipase A2 inhibitor, cyclosporin A (10 microM) and the lipoxygenase and cyclo-oxygenase inhibitor, eicosatetraynoic acid (ETYA, 20 microM) and nordihydroguairetic acid (NDGA, 20 microM) did not alter i.p.s.ps or hyperpolarizations to UK 14304. 4. Exogenously applied arachidonic acid (1-300 microM) did not mimic the i.p.s.p. or the hyperpolarization to UK 14304. 5. We conclude that arachidonic acid or its eicosanoid metabolites produced by phospholipase A2 stimulation are unlikely to be involved in the receptor G-protein coupled activation of potassium currents in submucosal neurones. The inhibition of the noradrenaline-induced hyperpolarization by quinacrine and 4-BPB is most likely due primarily to blockade of the basal inwardly rectifying potassium conductance present in these neurones.
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PMID:Effects of phospholipase A2 inhibitors on coupling of alpha 2-adrenoceptors to inwardly rectifying potassium currents in guinea-pig submucosal neurones. 790 74

We used electrophysiological methods in a slice preparation to study the mechanisms of somatostatin (SS) effects on hippocampal pyramidal neurons. SS hyperpolarizes hippocampal pyramidal neurons in part by augmenting the time- and voltage-dependent M-current (IM), which has been shown to be reduced by muscarinic agonists. The SS effects are abolished by the phospholipase A2 inhibitors 4-bromophenacyl bromide and quinacrine. Arachidonic acid (AA) mimics all the effects of SS on hippocampal pyramidal neurons. The effects of AA and SS on IM are blocked by the lipoxygenase inhibitor nordihydroguaiaretic acid but not by the cyclooxygenase inhibitor indomethacin. Prostaglandins E2, F2 alpha, and I2 do not increase IM. However, the specific 5-lipoxygenase inhibitors 5,6-methanoleukotriene A4 methylester and 5,6-dehydroarachidonic acid both blocked the IM-augmenting action of either SS or AA. Leukotriene C4 (but not leukotriene B4) increases IM to the same extent as AA. IM was not altered by the 12-lipoxygenase product 12-hydroperoxyeicosatetraenoic acid, and SS effects were not altered by the 12-lipoxygenase inhibitor baicalein. These data implicate 5-lipoxygenase metabolite(s) (probably leukotriene C4) as a mediator for the IM-augmenting effect of SS. In addition, when the IM effect is blocked by lipoxygenase inhibitors, both SS and AA elicit another outward current that is not blocked by either lipoxygenase or cyclooxygenase inhibitors, suggesting a direct role of AA itself distinct from the IM effect. SS did not alter significantly Ca(2+)-dependent action potentials or, in whole-cell recordings, inward currents likely to represent high-threshold Ca2+ currents. The combined results of these studies suggest that SS hyperpolarizes hippocampal neurons by two mechanisms, both mediated through the AA system. However, one mechanism (IM) involves a metabolite of AA and is most effective at slightly depolarized potentials, whereas the other may involve AA itself and be more effective at membrane potentials near rest.
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PMID:Somatostatin inhibition of hippocampal CA1 pyramidal neurons: mediation by arachidonic acid and its metabolites. 809 29

In mucosa-bearing organs with inherent lymphoid populations, classical modes for control of the immune response may be augmented by products of extrinsic sensory afferent nerve endings which arborize through the lamina propria compartment containing large numbers of T and B lymphocytes. Therefore, we sought to determine the role of neuropeptides (substance P, vasoactive intestinal peptide, and somatostatin) in immune response regulation by using a homogeneous line of T lymphocytes (AO40.1 hybrid), whose activation is driven by a specific Ag (OVA) and where the end point (IL-2 release) could not be contributed to by accessory or other cells. IL-2 was quantitated by the rate of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolism with the use of a murine CD4+ IL-2-dependent T lymphocyte line, and dose-response effects of each neuropeptide were examined over a broad concentration range (10(-14)-10(-6) M) encompassing that regarded as physiologic. Vasoactive intestinal peptide stimulated IL-2 release at low concentrations with a marked effect at 10(-14) M that gradually returned to control levels by 10(-7) M. Somatostatin was associated with a substantial augmentation of AO40.1 T lymphocyte IL-2 release at 10(-10) to 10(-8) M concentrations, whereas substance P demonstrated a stimulatory effect only at high concentrations (10(-9) to 10(-6) M). Concomitant [3H]thymidine uptake studies suggested that changes in cell proliferation or viability did not account for neuropeptide-induced effects in our system. With several exceptions, similar results were found with mitogen (Con A)-stimulated AO40.1 cells and human colonic lamina propria mononuclear cells. It was concluded that the three study neuropeptides, over a broad range of concentrations, have profound stimulatory (and occasionally inhibitory) effects upon the function of a cloned T lymphocyte hybrid cell responding to specific Ag and that these events may reflect those of Ag-driven mucosal T lymphocytes exposed to neuropeptides in vivo.
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PMID:Modulation of T lymphocyte function by neuropeptides. Evidence for their role as local immunoregulatory elements. 851 59

The involvement of lateral hypothalamic area (LHA) neurons in the regulation of blood calcium homeostasis was investigated in unanesthetized rats. The microinjection of the gamma-aminobutyric acid A receptor antagonist bicuculline methiodide (BM, 4-40 ng x 0.5 microl(-1) x 5 min(-1)) into the LHA decreased the blood concentration of ionized calcium. Total serum calcium also decreased after the BM injection. This hypocalcemic effect was eliminated by a bilateral vagotomy of the gastric branches. An intravenous injection of atropine methyl bromide (a muscarinic antagonist), nadolol (a beta-adrenergic blocker), or ranitidine (a histamine H2 blocker) suppressed the BM-induced hypocalcemia, whereas phenoxybenzamine (an alpha-adrenergic blocker) proved to be ineffective. Although the intra-LHA injection of BM increased the serum gastrin, which is known to have a hypocalcemic effect, neither secretin nor somatostatin (gastrin-release inhibitors) blocked the hypocalcemic response. These results suggest that the hypocalcemia observed after the excitation of LHA neurons was mediated by muscarinic, beta-adrenergic, and histamine H2 receptors through the gastric vagus.
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PMID:Lateral hypothalamic injection of GABA(A) antagonist induces gastric vagus-mediated hypocalcemia in the rat. 936 16

Radiolabeling of the somatostatin analog octreotide was attempted with p-[18F]fluorophenacyl bromide ([18F]FPB). Following these unsuccessful trials, the reactivity of FPB was studied using benzyl mercaptan, phenyl acetic acid, benzyl alcohol, and benzyl amine as model compounds for amino acid functional groups. Structure and purity of products, relative reactivity of FPB in competition reactions, and radiolabeling experiments are described. In addition, improvement in labeling efficiency of HSA using [18F]FPB was achieved by pretreatment with 2-iminothiolane.
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PMID:Reactivity of p-[18F]fluorophenacyl bromide for radiolabeling of proteins and peptides. 937 25

The tumorigenesis of insulinomas is unclear. Hyperglycemia has been found in many short term experiments to be one of the strongest stimuli for proliferation of the pancreatic beta-cells. After isologous islet transplantation into the livers of streptozotocin-diabetic rats it has been shown by our group that the proliferative activity of islet graft epithelial cells is strongly increased in a hyperglycemic environment (low-number islet transplantation) compared with normoglycemic conditions (high-number islet transplantation). The aim of this study was to investigate the long-term fate of these hyperproliferative islet grafts. 66 out of 91 streptozotocin-diabetic male Lewis rats persisted in a mild diabetic state after transplantation of 250-450 islets (main group), 25 animals became normoglycemic immediately after transplantation of 1000-2000 islets (control group). 5-Bromo-2'-desoxyuridine was administered prior to sacrifice. For the determination of the proliferative activity of the different cell types immunohistochemistry for insulin, glucagon and somatostatin was combined with a 5-Bromo-2'-desoxyuridine immunohistochemistry. Six animals of the main group developed insulinomas in their livers between 18 and 24 months after islet transplantation (i.e. 18% of the animals which lived more than 18 months after transplantation). The insulinomas induced severe hypoglycemia (12-36 mg/dl blood glucose), and the tumor cells showed a high proliferative activity, a positive immunoreactivity for insulin, and typical electron dense granules. The normoglycemic control group animals did not develop endocrine tumors. This study shows for the first time that insulinomas develop in transplanted islets of Langerhans under the influence of the long-term proliferative stimulus hyperglycemia.
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PMID:[Insulinoma originating from transplanted pancreatic cells after low dose portal embolic islet transplantation in streptozotocin diabetic rats]. 947 68


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