UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular calcium [Ca2+]i acts as an important intracellular messenger system for secretion and synthesis, cell growth and differentiation. In order to demonstrate definitively that a change in [Ca2+]i is responsible for a physiological event, one has to measure [Ca2+]i directly within intact cells and correlate the time course of any [Ca2+]i changes with the biological response. Measurement of [Ca2+]i was done in a single cell preloaded with fluorescent Ca indicator fura2 using a fluorescent unit (lonoquant) consisting of an inverted microscope (Zeiss IM 35) equipped with a mercury lamp and a rotating filter wheel containing filters at wavelengths of 340 and 380 nm. Cells were alternately excited and emission signals of fura 2-loaded cells were collected by a photomultiplier and recorded on-line on a computer screen. As a model system, the rat C-cell carcinoma cell line rMTC 6-23 secreting calcitonin was used. An acute elevation of extracellular calcium resulted in an increase in [Ca2+]i within 5 sec and rapid release of preformed calcitonin. This tight linkage between extracellular calcium and [Ca2+]i is mediated via Ca influx through voltage-dependent Ca channels. These channels are modulated by intracellular cAMP, yielding a rhythmic oscillation of [Ca2+]i, as well as by extracellular somatostatin blocking the Ca channel and the increase of [Ca2+]i via a pertussis toxin sensitive Gi protein. The change in [Ca2+]i is associated with changes in calcitonin secretion, confirming the stimulus secretion coupling via voltage-dependent Ca channels in C-cells.
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PMID:Measurement of free cytosolic calcium in single cells: method and application. 135 76

The effect of somatostatin on cAMP accumulation and calcitonin secretion in C-cells of the rat medullary thyroid carcinoma cell line rMTC 6-23 was investigated. Intracellular cAMP accumulation as well as calcitonin secretion could be dose-dependently stimulated by rat growth hormone releasing factor (rGRF). The long-acting somatostatin analogue octreotide inhibited rGRF-stimulated cAMP accumulation and calcitonin secretion dose dependently but failed to block 8-bromo-cAMP-stimulated calcitonin secretion. The inhibitory effect of octreotide on rGRF-induced calcitonin secretion was partially abolished by pretreating the cells with pertussis toxin. The octreotide effect was not due to changes in the degradation of cAMP, as it was similarly seen in the presence of isobutylmethylxanthine. Thus we conclude that pertussis toxin-sensitive G-proteins are involved in the cAMP-mediated regulation of calcitonin secretion in C-cells.
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PMID:Inhibitory effect of somatostatin on cAMP accumulation and calcitonin secretion in C-cells: involvement of pertussis toxin-sensitive G-proteins. 135 52

We have characterized a G-protein-coupled glutamate receptor in primary cultures of striatal neurons. Glutamate, quisqualate, or trans-1-aminocyclopentane-1,3-dicarboxylate inhibited by 30-40% either forskolin-stimulated cAMP production in intact cells or forskolin plus vasoactive intestinal peptide-activated adenylyl cyclase assayed in neuronal membrane preparations. These inhibitory effects were suppressed after treatment of striatal neurons with Bordetella pertussis toxin, suggesting the involvement of a heterotrimeric guanine nucleotide-binding protein (G protein) of the G(i)/G(o) subtype. The pharmacological profile of this glutamate receptor negatively coupled to adenylyl cyclase was different from that of the metabotropic Qp glutamate receptor coupled to phospholipase C in striatal neurons and from that of the recently cloned "mGluR2" glutamate receptor, which is negatively coupled to adenylyl cyclase when expressed in non-neuronal cells.
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PMID:Characterization of a metabotropic glutamate receptor: direct negative coupling to adenylyl cyclase and involvement of a pertussis toxin-sensitive G protein. 135 3

Somatostatin and somatostatin receptors are transiently expressed in the immature rat cerebellar cortex but virtually undetectable in the cerebellum of adults. Although somatostatin binding sites have been visualized during the postnatal period in the external granule cell layer, the type of cell that expresses somatostatin receptors has never been identified; thus, the potential function of somatostatin in the developing cerebellum remains unknown. In the present study, we have taken advantage of the possibility of obtaining a culture preparation that is greatly enriched in immature cerebellar granule cells to investigate the presence of somatostatin receptors and the effect of somatostatin on intracellular messengers on cerebellar neuroblasts in primary culture. Autoradiographic labeling revealed the occurrence of a high density of binding sites for radioiodinated Tyr-[D-Trp8]somatostatin-(1-14) on 1-day-old cultured immature granule cells. Saturation and competition studies showed the existence of a single class of high-affinity binding sites (Kd = 0.133 +/- 0.013 nM, Bmax = 3038 +/- 217 sites per cell). Somatostatin induced a dose-dependent inhibition of forskolin-evoked cAMP formation (ED50 = 10 nM), and this effect was prevented by preincubation of cultured immature granule cells with pertussis toxin. Somatostatin also caused a marked reduction of intracellular calcium concentration. These results show the presence of functionally active somatostatin receptors on immature granule cells. Our data suggest the possible involvement of somatostatin in the regulation of proliferation and/or migration of neuroblasts during the development of the cerebellar cortex.
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PMID:Somatostatin receptors are expressed by immature cerebellar granule cells: evidence for a direct inhibitory effect of somatostatin on neuroblast activity. 135 66

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

A number of diverse signaling pathways can be activated by G-protein coupled receptors. However, the factors involved in selection of a particular transduction pathway by a single receptor are not well understood. We are attempting to address this issue utilizing the alpha 2-adrenergic receptor (alpha 2-AR) subfamily as a representative model system. In this report, we demonstrate that the cellular response mediated by an alpha 2-AR subtype is cell-specific and thus depends on its environment. Receptor coupling to adenylylcyclase was determined following stable expression of the rat alpha 2B- and alpha 2D-AR subtypes in three functionally distinct cell types (NIH-3T3 fibroblasts, DDT1 MF-2 smooth muscle cells, and the pheochromocytoma cell line PC-12). When the receptor subtype gene is expressed in NIH-3T3 and DDT1 MF-2 cells, receptor activation inhibits basal and forskolin-induced increases in cellular cAMP. However, in PC-12 transfectants the same receptor subtype actually increases basal cAMP and augments the effect of forskolin. Potentiation of the forskolin effect in PC-12 cells is insensitive to pertussis toxin but is blocked by loading the cells with BAPTA (bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid) which minimizes changes in Ca2+i by calcium chelation. These data and the functional demonstration of a Ca2+/calmodulin-sensitive adenylylcyclase in PC-12 but not NIH-3T3 and DDT1 MF-2 cells, suggests that the cell-specific effects of epinephrine are due to receptor coupling to both different G-proteins and types of adenylylcyclase.
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PMID:Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. III. Coupling of alpha 2-adrenergic receptor subtypes in a cell type-specific manner. 135 86

The mitogenic effect of extracellular ATP on porcine aortic smooth muscle cells (SMC) was examined. Stimulation of [3H]thymidine incorporation by ATP was dose-dependent; the maximal effect was obtained at 100 microM. ATP acted synergistically with insulin, IGF-1, EGF, PDGF, and various other mitogens. Incorporation of [3H]thymidine was correlated with the fraction of [3H]thymidine-labeled nuclei and changes in cell counts. The stimulation of proliferation was also determined by measurement of cellular DNA using bisbenzamide and by following the increase of mitochondrial dehydrogenase protein. The effect of ATP was not due to hydrolysis to adenosine, which shows synergism with ATP. ATP acted as a competence factor. The mitogenic effect of ATP, but not adenosine, was further increased by lysophosphatidate, phosphatidic acid, or norepinephrine. The inhibitor of adenosine deaminase, EHNA, stimulated the effect of adenosine but not ATP. The adenosine receptor antagonist theophylline depressed adenosine-induced mitogenesis. ADP and the non-hydrolyzable analogue adenosine 5'-[beta, gamma-imido]triphosphate (AMP-PNP) were equally mitogenic. Thus extracellular ATP stimulated mitogenesis of SMC via P2Y purinoceptors. The mechanism of ATP acting as a mitogen in SMC was further explored. Extracellular ATP stimulated the release of [3H]arachidonic acid (AA) and prostaglandin E2 (PGE2) into the medium, and enhanced cAMP accumulation in a dose-dependent fashion similar to ATP-induced [3H]thymidine incorporation. Inhibitors of the arachidonic acid metabolism pathway, quinacrine and indomethacin, partially inhibited the mitogenic effect of ATP but not of adenosine. Pertussis toxin inhibited ATP-stimulated DNA synthesis, AA release, PGE2 formation, and cAMP accumulation. Down-regulation of protein kinase C (PKC) by long-term exposure to phorbol dibutyrate (PDBu) partially prevented stimulation of DNA synthesis and activation of the AA pathway by ATP. The PKC inhibitor, staurosporine, antagonized mitogenesis stimulated by ATP. No synergistic effect was found when PDBu and ATP were added together. Therefore, a dual mechanism, including both arachidonic acid metabolism and PKC, is involved in ATP-mediated mitogenesis in SMC. In addition, ATP acted synergistically with angiotensin II, phospholipase C, serotonin, or carbachol to stimulate DNA synthesis. Finally, the possible physiological significance of ATP as a mitogen in SMC was further studied. The effect of endothelin and heparin, which are released from endothelial cells, on ATP-dependent mitogenesis was investigated. Extracellular ATP acted synergistically with endothelin to stimulate a greater extent of [3H]thymidine incorporation than was seen with PDGF plus endothelin. Heparin, believed to have a regulatory role, partially inhibited the stimulation of DNA synthesis caused both by ATP and PDGF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extracellular ATP and ADP stimulate proliferation of porcine aortic smooth muscle cells. 135 98

Octreotide (SMS), a somatostatin analogue, is an established antigrowth peptide, but it does not effectively inhibit the growth of insulinoma cells. In order to study the mechanisms that underlie this apparent lack of an antiproliferative effect on insulinoma tumor cells we established the rat insulinoma cell line, RINm5F, in culture. Cells in culture were tested by incubation in media with and without SMS. To study tritiated [3H]-thymidine incorporation into extracted DNA (TTID), 2 muCi/well of 3H was added for 24 hr, and cells were harvested and assayed for TTID (cpm/microgram DNA). Insulin (IRI) and intracellular cAMP (cAMPi) were measured by RIA. To study the effects of SMS on insulin secretion, conditioned media were sampled after 24 hr. To study the effects of cAMPi, conditioned medium was used to extract cAMPi following incubation with SMS for 15 min. Increasing concentrations of SMS had no significant effect on TTID in the presence of 1% FBS. Trypan blue exclusion tests showed > 90% viable cells throughout all stages of these experiments. There were no significant differences in cell numbers and protein content in the presence of SMS. There was a significant decrease in the secretion of insulin and intracellular cAMP levels in response to 50 nM SMS. However, SMS significantly inhibited TTID in RINm5F cells following a 4-hr pretreatment with pertussis toxin (PT) (23553 +/- 1747 vs 20635 [cpm/microgram DNA] +/- 1983 [SEM], P < 0.01). We conclude that the inhibition of insulin secretion by SMS is associated with an attenuation of cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of somatostatin action in RINm5F cells in culture: preliminary evidence for possible altered G protein function. 135 94

The mechanisms by which somatostatin inhibits hormone release are complex and involve, among other things, reduction of both intracellular cAMP and intracellular calcium. We studied the influence of the long-acting somatostatin analogue octreotide on norepinephrine (NE)-induced changes in intracellular calcium ([Ca2+]i) in fura-2 loaded single cells of a rat medullary carcinoma cell line, rMTC 6-23. Increases in the extracellular calcium concentration ([Ca2+]e) induced a sudden rise in [Ca2+]i which could be blocked by EGTA or the calcium channel blocker verapamil. NE evoked a similar increase in [Ca2+]i, which also could be blocked by the addition of EGTA or verapamil. Octreotide prevented or reversed the NE-induced increase in [Ca2+]i. Pretreatment of the cells with pertussis toxin abolished the inhibitory effect of octreotide. Thus we conclude that the NE-induced rise in [Ca2+]i is due to an influx of [Ca2+]e, most probably through voltage-dependent calcium channels. Octreotide inhibits the NE-stimulated rise in [Ca2+]i by a pertussis toxin-sensitive G-protein, most probably through a direct effect on NE-activated calcium channels.
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PMID:Somatostatin inhibits the norepinephrine-activated calcium channels in rMTC 6-23 cells: possible involvement of a pertussis toxin-sensitive G-protein. 136 Jan 85

The effect of the somatostatin analog octreotide on cAMP-mediated calcitonin (CT) secretion and cAMP accumulation in C-cells was investigated. Glucagon stimulated cAMP accumulation and CT secretion with a maximal effect at a concentration of 10(-6) M. The cAMP antagonist RpcAMPs blocked the glucagon-induced CT secretion down to control levels. Therefore, no other second messengers seem to be involved in glucagon-stimulated CT secretion. Octreotide in increasing doses (10(-9) to 10(-6) M) inhibited cAMP accumulation and CT secretion with a maximal effect at a concentration of 10(-7) (40% and 29% of control values, respectively). Pretreatment of the cells with 100 ng/mL pertussis toxin for 24 hours abolished the inhibitory effect of octreotide on cAMP accumulation and CT secretion (82% and 58% of control values, respectively). Similar results were obtained under the influence of the phosphodiesterase inhibitor IBMX. Therefore, we conclude that somatostatin modulates adenylate cyclase-coupled CT secretion in C-cells via a pertussis toxin-sensitive G-protein possibly in an autocrine/paracrine way.
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PMID:Somatostatin acts via a pertussis toxin-sensitive mechanism on calcitonin secretion in C-cells. 136 26

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