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)

When applied to the skin, phorbol esters (PEs) elicit signs of acute inflammation, suggesting they may induce the release of mediators from mast cells. Therefore, we have studied the effects of PEs on purified rat peritoneal and thoracic mast cells both alone and in conjunction with the calcium ionophore, A23187, and various other secretagogues that interact with immunoglobulin E (e.g., anti-IgE and Con A) or other cell surface receptors, e.g., somatostatin and compd 48/80. PEs alone caused little or no release of histamine. However, the PE 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 ng/ml) tremendously potentiated release induced by the calcium ionophore A23187, reducing the EC50 for A23187 from 832 ng/ml to 56 ng/ml. In the presence of suboptimal A23187 (50 ng/ml), only active tumor promoting PEs elicited histamine release. The EC50 values of the various active PEs were: TPA 5 ng/ml; 4 beta-PDD, 83 ng/ml; and 4-O-methyl-TPA, 807 ng/ml, with maximal histamine release ranging from 54 to 80%. TPA synergistically enhanced stimulation of histamine release by anti-IgE and Con A over the entire concentration-response range. In contrast, this synergism was absent when cells were stimulated with somatostatin and compd 48/80. Phorbol esters may act by increasing the activity of a calcium/phospholipid-dependent protein kinase (Ca/PL-PK). Mast cells do have Ca/PL-PK activity, and TPA in the presence of suboptimal A23187 induces protein phosphorylation comparable with other secretagogues. These results suggest that in the purified mast cell, PE-induced mediator release increases the sensitivity of release mechanisms for calcium, acts syngergistically with secretagogues interacting with IgE, and as suggested from structure-activity relationships, occurs via a specific mechanism of action perhaps involving the Ca/PL-PK.
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PMID:Characterization of the effects of phorbol esters on rat mast cell secretion. 257 54

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

We studied five cases of poorly differentiated follicular or papillary thyroid carcinomas. Immunohistochemical study revealed numerous ACE positive cells, also positive for calcitonin, ACTH, somatostatin or several of these peptides. These tumors containing both vesicular component and parafollicular cells are endocrine tumors of "mixed" or "intermediate" type. The diagnosis must be confirmed by immunohistochemistry but can be suggested by histological findings: abundant fibrous stroma, trabeculovesicular pattern, and swelled moderately acidophilic cells neighbouring vesicular cells. These facts argue in favor of a common-embryological origin of vesicular and parafollicular cells from ultimobranchial undifferentiated cells. Nevertheless such tumors must take place in thyroid neoplasia's classifications and an appropriate terminology remains to be precised.
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PMID:["Mixed' (follicular and parafollicular) carcinomas of the thyroid. Histological and immunocytological study of 5 cases]. 271 68

We undertook these studies to examine the mechanisms by which carbachol inhibits somatostatin release. For these studies, we utilized cultured D-cells isolated from the canine gastric fundus. Carbachol inhibited somatostatin release induced by both pentagastrin and 12-O-tetradecanoyl-phorbol-13-acetate but did not alter the redistribution of protein kinase C induced by these agents. In contrast, carbachol diminished the increase in D-cell cytosolic free calcium levels ([Ca2+]i) induced by pentagastrin, and this effect was no longer evident after pretreatment of D-cells with pertussis toxin. Although carbachol by itself had no effect on [Ca2+]i, after pretreatment of D-cells with pertussis toxin, carbachol both enhanced [Ca2+]i and stimulated somatostatin release. These data indicate that carbachol activates signals in D-cells that result in both increase and decrease in [Ca2+]i. The latter effect, which appears to be mediated via a pertussis toxin-sensitive guanine nucleotide binding protein, may be one mechanism responsible for cholinergic inhibition of somatostatin release.
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PMID:Carbachol inhibits stimulant-induced increases in fundic D-cell cytosolic Ca2+ concentration. 276 14

GH secretion and mRNA levels were measured in cultured cells obtained from six human pituitary somatotroph tumors to investigate their hormonal and intracellular regulation. The responses were variable between tumors, but, in general, mRNA levels were less responsive than GH release to in vitro manipulation. GH-releasing factor [GRF-(1-29) amide; 10 nM] increased GH release and mRNA levels in three of four tumors tested to 30-97% above control values, but the fourth tumor was unresponsive. Somatostatin (1 microM) inhibited GH release significantly in four of the six cases, to 35-79% of control levels, but had no inhibitory effect on GH mRNA accumulation, in contrast to earlier studies on rat pituitary tissue. Bromocriptine (100 nM) likewise inhibited GH release (50-75% of control), but not GH mRNA levels, in the four tumors tested. Forskolin (10 microM; used to activate adenylate cyclase) stimulated GH release and mRNA levels in the two cases that responded most clearly to GRF, but had no significant effect in the other tumors; however, the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (100 nM) had no consistent effect on mRNA levels despite stimulating secretion in four of six cases. Thus, there was considerable variation in responses among the tumors tested; however, the responsiveness to GRF was approximately paralleled by that to forskolin, consistent with the suggestion that adenylate cyclase activity and responsiveness are variable among these tumors. Furthermore, the divergent effects of somatostatin on GH release and mRNA suggest uncoupling between its receptor and transcriptional regulatory mechanisms.
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PMID:Regulation of growth hormone secretion and messenger ribonucleic acid accumulation in human somatotropinoma cells in vitro. 277 32

The mechanism of glucose-stimulated cyclic AMP accumulation in mouse pancreatic islets was studied. In the presence of 3-isobutyl-1-methylxanthine, both glucose and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, enhanced cyclic AMP formation 2.5-fold during 60 min of incubation. Both TPA-stimulated and glucose-stimulated cyclic AMP accumulations were abolished by the omission of extracellular Ca2+. The Ca2+ ionophore A23187 did not affect cyclic AMP accumulation itself, but affected the time course of TPA-induced cyclic AMP accumulation, the effect of A23187 + TPA mimicking the time course for glucose-induced cyclic AMP accumulation. A 24 h exposure to TPA, which depletes islets of protein kinase C, abolished the effects of both TPA and glucose on cyclic AMP production. Both TPA-induced and glucose-induced cyclic AMP productions were inhibited by anti-glucagon antibody, and after pretreatment with this antibody glucose stimulation was dependent on addition of glucagon. Pretreatment of islets with TPA for 10 min potentiated glucagon stimulation and impaired somatostatin inhibition of adenylate cyclase activity in a particulate fraction of islets. Carbamoylcholine, which is supposed to activate protein kinase C in islets, likewise stimulated cyclic AMP accumulation in islets. These observations suggest that glucose stimulates islet adenylate cyclase by activation of protein kinase C, and thereby potentiates the effect of endogenous glucagon on adenylate cyclase.
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PMID:Stimulation by glucose of cyclic AMP accumulation in mouse pancreatic islets is mediated by protein kinase C. 284 66

Gastrinoma cells from surgical specimens of a primary pancreatic tumor and an hepatic metastasis in two patients with a Zollinger-Ellison syndrome were grown and subcultured for 7 mo. Cultured cells displayed a strong reactivity to heptadecapeptide gastrin antibody and maintained an ultrastructural appearance resembling that of the original tumor cells with the presence of secretory granules of variable size and electron density. Cultured cells also showed the ability to secrete immunoreactive gastrin, and this secretion was further concentration-dependently stimulated by secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin (10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than 0.05). This stimulation occurred in the absence of extracellular Ca2+ and was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin analogue, somatostatin-(201-995), did not alter basal gastrin release but inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP (10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early time intervals of incubation. Furthermore the phorbol ester derivative, 12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin release (10 times the basal value). We conclude that gastrinoma cells can be cultured over an extended period with maintenance of their capacity to secrete gastrin in response to various hormones and mediators.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastrin secretion by gastrinoma cells in long-term culture. 284 43

Addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) to S49 lymphoma cells (wild type and a cyclic AMP-dependent protein kinase-lacking clone) has little effect alone but doubles accumulation of cyclic AMP in response to isoproterenol. The effect is immediate and has an apparent affinity and order of potency characteristic of the activation of protein kinase C by phorbol esters. Enhancement does not reflect an altered time course of the beta-adrenergic response, enhanced affinity of the cellular beta-receptor for agonist, or decreased degradation and export of cellular cyclic AMP. Reduction of the beta-adrenergic response by somatostatin does not remove the effect of TPA nor does TPA abolish the effect of somatostatin. Phorbol ester enhances cyclic AMP accumulation in response to cholera toxin in wild type and UNC clones but not in H21a or cyc-. TPA also enhances cAMP accumulation in response to forskolin in wild type cells. The effect of TPA is stable to rapid preparation of membranes. In adenylate cyclase assays on membranes from cells treated with TPA, the activation by guanosine 5'-(beta, gamma-imino)triphosphate is enhanced by 40% with no change in lag time; the effect of beta-agonist plus Gpp(NH)p is similarly enhanced; activation by Mn2+ is unchanged. We conclude that phorbol ester facilitates the productive interaction of the alpha subunit of the transducer protein Gs with the catalytic unit of adenylate cyclase, hypothetically via an action of protein kinase C.
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PMID:Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Putative effect of C kinase on alpha s-GTP-catalytic subunit interaction. 285 14

The main purpose of the present study was to characterize the tissue and releasable molecular forms of somatostatin-28[1-12]-like immunoreactivity (S-28[1-12]LI) in rat median eminence (ME) fragments and to compare them with somatostatin-14-like immunoreactivity (S-14 LI) forms. Acetic acid extracts of ME were fractionated on Sephadex G-50 columns (in 6 M urea). The column eluate was monitored for S-28[1-12] LI by RIA with antibody R21 which detects S-28[1-12], S-28, and higher molecular weight forms of S-28[1-12] LI, but not S-14. The S-14 LI RIA utilized recognizes S-14, S-28, and prosomatostatin (pro-S). Rat ME contained 221 +/- 25 pmol S-14 LI/mg protein and 407 +/- 51 pmol S-28[1-12] LI/mg protein. By gel filtration S-14 LI was resolved into three peaks corresponding to S-14, S-28, and a higher mol wt form (14,000) corresponding to pro-S. S-28[1-12] LI consisted of at least five forms corresponding to pro-S, S-28, S-28[1-12], a form which represented pro-S without the S-14 sequence, and a form slightly smaller than S-28[1-12]. Pools of 20 ME incubated in 56 mM K+ solution showed 4.6-fold Ca++-dependent release of S-14 LI and 4-fold release of S-28[1-12] LI. Gel chromatographic analysis of the released material showed all three tissue S-14 LI forms and each of the tissue S-28[1-12] LI forms. HPLC analysis and RIAs further confirmed the release of S-14, S-28, S-28[1-12], and the S-28[1-12] LI form smaller than S-28[1-12]. These data suggest the presence of at least six molecular forms of somatostatin in ME. The release of this large number of peptides, presumably from mature secretory granules in ME in response to depolarization, suggests that they are products of the normal posttranslational processing of pro-S.
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PMID:Characterization of tissue and releasable molecular forms of somatostatin-28[1-12]-like immunoreactivity in rat median eminence. 285 91

Cerebral cortex slices from mice were used to investigate the variations of lipid metabolism by somatostatin. Somatostatin decreased [14C]acetate incorporation into all lipid fractions significantly. Likewise, the peptide evoked a decrease of triglyceride lipase activity. The incorporation of [32P]orthophosphate into phospholipids was diminished by somatostatin. These results add more information about the effects of somatostatin in cerebral cortex.
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PMID:Actions of somatostatin on lipid metabolism in mouse cerebral cortex slices. 286 17


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