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)

The initial events in signal transduction in insulin-secreting cells are summarized in FIGURE 8. Both nutrient stimuli, such as glucose and amino acids and the muscarinic agonist carbachol (carbamylcholine) raise [Ca2+]i. Although the rise in [Ca2+]i precedes the stimulation of insulin release, it is not a moment-to-moment regulator of release. The metabolizable fuel stimuli cause Ca2+ influx through voltage-dependent Ca2+ channels following depolarization of the membrane potential. In contrast, carbachol, which does not depolarize, elicits Ptd Ins 4,5-P2 hydrolysis, a reaction catalyzed by phospholipase C. The generation of Ins 1,4,5-P3 in this instance is Ca2+ independent, but appears to involve a GTP-binding protein. However, this protein is not a substrate for pertussis toxin. The levels of Ins 1,4,5-P3, which releases Ca2+ from an ATP-dependent Ca2+ pool of the endoplasmic reticulum, are increased prior to the rise in [Ca2+]i. The mitochondria may take up Ca2+ after large increases in [Ca2+]i. A previously proposed second messenger, arachidonic acid, is much less selective than Ins 1,4,5-P3 in that it releases Ca2+ from mitochondria as well as from the endoplasmic reticulum in a slow and irreversible manner. As Ins 1,4,5-P3 is also generated during glucose stimulation of islets, albeit in a Ca2+-dependent manner, this metabolite could mediate not only the action of carbachol but also contribute to amplifying the [Ca2+]i rise in response to glucose.
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PMID:Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists. 310 54

Employing [32P]ADP-ribosylation by pertussis toxin we have identified a G protein that is located in the rough endoplasmic reticulum of canine pancreas and therefore termed it GRER. Identification of GRER is based on the following data. A 41-kDa polypeptide was the only polypeptide that was [32P]ADP-ribosylated by pertussis toxin in pancreas rough microsomes. Guanosine 5'-(gamma-thio)triphosphate (GTP gamma S) and 1 mM ATP, 6 mM MgCl2, 10 mM NaF (AMF) inhibited ADP-ribosylation of this polypeptide. The [32P]ADP-ribosylated 41-kDa polypeptide was immunoprecipitated by antisera which specifically recognized the C-terminal residues of the alpha subunits of Gi and transducin, indicating that the 41-kDa polypeptide is immunologically related to the alpha subunits of heterotrimeric G proteins. Treatment with GTP gamma S resulted in a reduction in the sedimentation rate of the [32P]ADP-ribosylated, detergent-solubilized GRER. It also induced the release of the [32P]ADP-ribosylated 41-kDa polypeptide from rough microsomes in the absence of detergent, unlike ADP-ribosylated alpha subunits of plasma membrane-associated G proteins. These data are consistent with an oligomeric nature of GRER. The codistribution of GRER with an endoplasmic reticulum marker protein during subcellular fractionation and the lack of plasma membrane contamination of the rough microsomal fraction, combined with the isodensity of GRER with rough microsomes as well as the isodensity of GRER with "stripped" microsomes after extraction of rough microsomes with EDTA and 0.5 M KCl, localized GRER to the rough endoplasmic reticulum. Preliminary experiments suggest that GRER appears not to be involved in translocation of proteins across the rough endoplasmic reticulum membrane.
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PMID:Identification of a G protein in rough endoplasmic reticulum of canine pancreas. 314 6

Human leukocyte 5-lipoxygenase (EC 1.13.11.12) is unique among the human lipoxygenase not only in its requirement for free ionized calcium, but also in its regulation by a membrane-associated stimulatory factor, the 100,000 x g pellet. In the present study, phosphatidylcholine (PC) vesicles, in the absence of 100,000 x g pellet, exhibited a dose-dependent stimulatory activity on the 5-lipoxygenase, which was at least as effective as the 100,000 x g pellet. Furthermore, the enzyme was activated by isolated human neutrophil plasma membranes and to a lesser degree by endoplasmic reticulum. The chemoattractant peptide fMet-Leu-Phe (0.1 microM), GTP (10 microM), toxin from bacterium Bordetella pertussis (islet activating protein, 5 micrograms/ml) and their various combinations were unable to modulate the enzymatic activity of the 5-lipoxygenase. Stimulation of the 5-lipoxygenase by relatively low levels of free ionized calcium was observed both in the presence of the pellet and PC vesicles: maximal stimulation was seen at about 10 microM Ca2+. The human leukocyte leukotriene A4 synthase activity also exhibited a similar requirement for free calcium ions. The present study indicates that the membrane-associated stimulatory factor of the human leukocyte 5-lipoxygenase may be replaced by PC vesicles. Moreover, the 5-lipoxygenase and leukotriene A4 synthase activities require significantly lower Ca2+ levels for maximal activation than has been reported previously.
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PMID:Regulation of the human leukocyte 5-lipoxygenase: stimulation by micromolar Ca2+ levels and phosphatidylcholine vesicles. 338 74

1. In hepatocytes, epidermal growth factor (EFG) (a) increased the rate of 45Ca2+ exchange in cells incubated at 1.3 mM extracellular Ca2+, (b) increased the activity of glycogen phosphorylase a and the intracellular free Ca2+ concentration (measured with quin2) in a process dependent on the concentration of extracellular Ca2+, and (c) enhanced the increase in glycogen phosphorylase activity which follows the addition of Ca2+ to cells previously incubated in the absence of Ca2+. It is concluded that EGF stimulates plasma-membrane Ca2+ inflow. 2. The effects of the combination of EGF and vasopressin on the rate of 45Ca2+ exchange and on the rate of increase in glycogen phosphorylase activity were the same as those of vasopressin alone. 3. The amount of 45Ca2+ released by EGF from internal stores was about 30% of that released by vasopressin. No detectable increase in [3H]inositol mono-, bis- or tris-phosphate was observed after the addition of EGF to cells labelled with myo-[3H]inositol. 4. In hepatocytes isolated from rats treated with pertussis toxin, the effects of EGF and vasopressin on phosphorylase activity (measured at 1.3 mM-Ca2+) and on the rate of Ca2+ inflow (measured with quin2) were markedly decreased compared with those in normal cells. 5. Treatment with pertussis toxin did not impair the ability of vasopressin to release Ca2+ from internal stores, but decreased vasopressin-stimulated [3H]inositol polyphosphate formation by 50%. 6. It is concluded that the mechanism(s) by which vasopressin and EGF stimulate plasma-membrane Ca2+-inflow transporters in hepatocytes involves a GTP-binding regulatory protein sensitive to pertussis toxin, and does not require an increase in the concentration of inositol trisphosphate comparable with that which induces the release of Ca2+ from the endoplasmic reticulum.
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PMID:Evidence that a pertussis-toxin-sensitive substrate is involved in the stimulation by epidermal growth factor and vasopressin of plasma-membrane Ca2+ inflow in hepatocytes. 350 16

The distribution of large dividing lymph node or thoracic duct lymph cells, labeled in vitro with (3)H-thymidine, was studied in syngeneic recipient rats after intravenous injection. In most experiments the donor rats had been immunized with Bacillus pertussis 4 days earlier, but in some instances cells from nonimmunized donors were used. In smears, the labeled donor cells had the appearance of large lymphocytes or large pyroninophilic cells. By electronmicroscopy, the majority of labeled donor cells were seen to have only scanty endoplasmic reticulum. It was found that the labeled cells rapidly "homed" to lymphoid tissue and recirculated in the recipient, in a fashion resembling that of small lymphocytes. However, the distribution of labeled cells was found to depend upon the source of the donor cells. Cells from mesenteric lymph nodes or thoracic duct lymph showed a marked preferential accumulation in lymphoid tissue within or adjacent to the intestine, whereas cells from peripheral nodes accumulated preferentially in peripheral lymph nodes. Cells from any of these sources showed an equal tendency to accumulate in the white pulp of the spleen. Suspensions of small lymphocytes, labeled in vitro with (3)H-uridine, did not display a similar tendency to localize preferentially in lymphoid tissue in certain regions. It was also found that large dividing lymph node cells from donors immunized with an antigen (2,4-dinitrophenyl-bovine gamma globulin (DNP-BGG) or B. pertussis) showed a greater tendency to accumulate in a recipient lymph node containing that antigen than in the contralateral node. It was not determined whether the selective accumulation of large dividing lymphoid cells from different sources in lymphoid tissue of different regions in recipients was due to an antigen recognition mechansim or was the result of two different populations of cells with different "homing" mechanisms.
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PMID:The distribution of large dividing lymph node cells in syngeneic recipient rats after intravenous injection. 418 28

Streptolysin O-permeabilized cells incubated with a high concentration (5-10 mg/ml) of cytosolic proteins and ATP-generating system exhibit redistribution into the endoplasmic reticulum (ER) of Golgi integral proteins (mannosidase II, galactosyltransferase, TGN 38), detected by immunofluorescence. In addition, mannosidase II is detected in the ER of cells exposed to a high concentration of cytosolic proteins and processed for immunolectron microscopy by immunoperoxidase. The redistribution process requires ATP and is not affected by previous microtubule depolymerization. Ultrastructural observations indicate that Golgi disassembly occurs by budding of coated vesicles. This stage of the process is inhibited by GTP-gamma S, AIF(3-5), transducin beta gamma subunits, and mastoparan, indicating the involvement of trimeric G proteins. At a later stage, vesicles lose their coats and fuse with the ER. This part of the process does not occur in cells incubated at either 15 degrees C or 20 degrees C, or exposed to N-ethylmaleimide. In cells treated with either cholera or pertussis toxin Golgi redistribution into the ER shows a 50-fold lower requirement for cytosolic factors than in untreated cells. These data suggest a regulatory role for both alpha s and alpha i trimeric G proteins in the normal Golgi-ER retrograde transport taking place in intact cells.
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PMID:Trimeric G proteins regulate the cytosol-induced redistribution of Golgi enzymes into the endoplasmic reticulum. 761 93

This study investigated the underlying mechanisms of oxytocin (OT)-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in acutely dispersed myometrial cells from prepartum sows. A dose-dependent increase in [Ca2+]i was induced by OT (0.1 nM to 1 microM) in the presence and absence of extracellular Ca2+ ([Ca2+]e). [Ca2+]i was elevated by OT in a biphasic pattern, with a spike followed by a sustained plateau in the presence of [Ca2+]e. However, in the absence of [Ca2+]e, the [Ca2+]i response to OT became monophasic with a lower amplitude and no plateau, and this monophasic increase was abolished by pretreatment with ionomycin, a Ca2+ ionophore. Administration of OT (1 microM) for 15 sec increased inositol 1,4,5-trisphosphate (IP3) formation by 61%. Pretreatment with pertussis toxin (PTX, 1 microgram/ml) for 2 hr failed to alter the OT-induced increase in [Ca2+]i and IP3 formation. U-73122 (30 nM to 3 microM), a phospholipase C (PLC) inhibitor, depressed the rise in [Ca2+]i by OT dose dependently. U-73122 (3 microM) also abolished the OT-induced IP3 formation. Thapsigargin (2 microM), an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum, did not increase [Ca2+]i. However, it did time-dependently inhibit the OT-induced increase in [Ca2+]i. Nimodipine (1 microM), a voltage-dependent Ca2+ channel (VDCC) blocker, inhibited the OT-induced plateau by 26%. La3+ (1 mM), a nonspecific Ca2+ channel blocker, abrogated the OT-induced plateau. In whole-cell patch-clamp studies used to evaluate VDCC activities, OT (0.1 microM) increased Ca2+ current (ICa) by 40% with no apparent changes in the current-voltage relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocin induced a biphasic increase in the intracellular Ca2+ concentration of porcine myometrial cells: participation of a pertussis toxin-insensitive G-protein, inositol 1,4,5-trisphosphate-sensitive Ca2+ pool, and Ca2+ channels. 761 2

Membrane-bound GTP-binding (G) proteins mediate signal transduction in a variety of cell systems. The exact mechanisms of G proteins action are still under investigation but they appear to involve effectors located in the plasma membrane as well as in other parts of the cell. With this study, we investigated the cellular and ultrastructural localization of G protein subunits, and particularly of Go alpha, in normal rat anterior pituitaries and in estrone-induced rat adenomatous lactotrophs. We also evaluated the effects of Go alpha cellular redistribution in rat adenomatous lactotrophs following short-term exposure to dopamine (DA). Using the Protein A-gold (PAG) methodology, Go alpha was found to be present in the cysternae of the endoplasmic reticulum of normal pituitary cells and of adenomatous lactotrophs. In the latter, Go alpha could be co-localized with prolactin (PRL). By immunoblots, using specific antisera, significant amounts of Go alpha and Gs42 alpha, together with smaller amounts of Gi alpha, Gs47 alpha and G beta were found to be present in the uncontaminated supernatant fraction of adenomatous lactotrophs. Unexpectedly, exposure of the cells to DA induced a rapid and short-lived decrease in the cytosolic fraction of Go alpha and G beta associated with a decrease of PRL release. Since cytosolic Go alpha can be ADP-ribosylated by pertussis toxin (PT) and is therefore in a heterotrimeric form, our data suggest that the soluble Go protein may play a role during lactotrophs' exposure to an inhibitor of PRL release, perhaps through its relocalization after being internalized with the D2 receptor or by being used for interaction with intracellular and/or membrane-bound effectors.
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PMID:Cellular distribution of G protein Go alpha in pituitary lactotrophs: effects of dopamine. 798 76

Bone is a target tissue of androgens, but the mechanisms by which they act on bone are still unclear. This study examines the early (5-60 s) effects of 1 pM to 1 microM testosterone on cytosolic free Ca2+ concentration ([Ca2+]i) and inositol 1,4,5-trisphosphate (InsP3) and diacyglycerol (DAG) formation in confluent male rat osteoblasts. 10 pM to 10 nM testosterone increased [Ca2+]i within 5 s via Ca2+ influx as shown by the effects of EGTA and the Ca2+ channel blockers nifedipine and verapamil and via Ca2+ mobilization from the endoplasmic reticulum as shown by the effects of thapsigargin and neomycin. 10 pM to 10 nM testosterone increased InsP3 and DAG formation within 10 s. Testosterone immobilized on bovine serum albumin (testosterone (O-carboxymethyl)oxime/bovine serum albumin) and its derivative, (O-carboxymethyl)oxime, rapidly increased [Ca2+]i and InsP3 and DAG formation and were full agonists, although they were less potent than the free steroid. Cyproterone acetate, a nuclear antagonist, did not block the increase in [Ca2+]i and InsP3 and DAG formation induced by testosterone. Finally, neomycin and pertussis toxin totally abolished the effects of testosterone on InsP3 and DAG. These results suggest that male rat osteoblasts bear nongenomic unconventional cell-surface receptors for testosterone that belong to the class of the membrane receptors coupled to a phospholipase C via a pertussis toxin-sensitive G-protein.
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PMID:Androgens increase intracellular calcium concentration and inositol 1,4,5-trisphosphate and diacylglycerol formation via a pertussis toxin-sensitive G-protein. 812 34

The movement of newly synthesized proteins in the constitutive secretory pathway, from their site of synthesis in the endoplasmic reticulum to the cell surface or to intracellular destinations, requires an orderly sequence of transport steps between membrane-bound compartments. Until recently, the trafficking and secretion of proteins through this pathway was thought to occur as a relatively automatic, unregulated series of events. Recent studies show that protein trafficking in the constitutive secretory pathway requires GTP hydrolysis by families of GTP-binding proteins (G proteins), which at multiple steps potentially provide regulation and specificity for protein trafficking. Many monomeric G proteins are known to be localized and functional on membrane compartments in the constitutive secretory pathway. Now, members of the heterotrimeric G protein family have also been localized on intracellular membranes and compartments such as the Golgi complex. We have studied the localization and targeting of G alpha subunits to distinct membrane domains in polarized epithelial cells. The distribution of different G alpha subunits on very specific membrane domains in cultured epithelial cells and in epithelial cells of the kidney cortex, is highly suggestive of roles for these G proteins in intracellular trafficking pathways. One of these G protein subunits, G alpha i-3, was localized on Golgi membranes. Studies on LLC-PK1 cells overexpressing G alpha i-3 provided evidence for its functional role in regulating the transport of a constitutively secreted heparan sulfate proteoglycan through the Golgi complex. Inhibition or activation of heterotrimeric G proteins by pertussis toxin or by aluminium fluoride respectively, have provided further evidence for regulation of intracellular transport by pertussis toxin-sensitive G proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distribution and role of heterotrimeric G proteins in the secretory pathway of polarized epithelial cells. 814 3

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