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)

Akin to receptor inactivation with phenoxybenzamine (PBZ) (1 microM, 1 hr), treatment of anterior pituitary cells with 17 beta-estradiol (10 nM, 3 days) right-shifted the dose-response curve for inhibition of prolactin (PRL) secretion by the full agonist R-(-)-N-n-propylnorapomorphine (NPA) and reduced the maximal effect [EC50 (pM) and percent maximal effect: control, 25.4 and 81.2; PBZ, 115.3 and 57.9; 17 beta-estradiol, 358 and 58.6]. PBZ treatment of 17 beta-estradiol-pretreated cultures further reduced the maximal response but did not alter the EC50. Plots of receptor occupancy vs. response indicated a large receptor reserve for NPA (approximately 60%) in control cultures but its abolition by 17 beta-estradiol. 17 beta-Estradiol pretreatment elicited identical rightward shifts (4.5-fold) and similar reductions in maximal PRL inhibition by quinpirole and (+)-3-PPP, although these drugs were partial agonists with dissimilar efficacies relative to NPA (0.61 and 0.12, respectively) at presynaptic striatal D2 receptors. However, receptor inactivation experiments with (+)-3-PPP and quinpirole, and subsequent comparison of receptor occupancy vs. response plots, demonstrated that the relative efficacies of quinpirole and (+)-3-PPP were reversed in the striatum and anterior pituitary. In striatum, half-maximal response to quinpirole and (+)-3-PPP required 6.2 and 30% receptor occupancy, respectively, whereas 25.6 and 9.6% occupancy was required in the pituitary. Pertussis toxin treatment (10 ng/ml, 24 hr) produced large shifts in the dose-response curves for all three agonists (8.4-21.9-fold), but was distinguished from the effects of both PBZ and 17 beta-estradiol by a significant (P < .001) decrease in the slope factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of receptor inactivation, 17 beta-estradiol and pertussis toxin on dopaminergic inhibition of prolactin secretion in vitro. 135 7

Previous studies have shown that the injection of estrogen into immature rats leads to an influx of leukocytes into the uterus. Using immunoperoxidase staining and monoclonal antibodies, we have characterized the nature of the infiltrating leukocytes in frozen sections of immature rat uteri obtained following the injection of estrogen, estrogen plus pertussigen, and the antiestrogen LY117018. Estradiol treatment for 2 days resulted in a significant increase in the number of uterine eosinophils, CD4 (W3/W25)-positive helper/inducer T lymphocytes, macrophages (MRC OX-42-positive cells), and Ia (MRC OX-6)-positive cells. In contrast, estradiol treatment failed to elicit a significant increase in the number of CD8 (MRC OX-8)-positive uterine cytotoxic/suppressor T lymphocytes and/or natural killer cells, as well as MAR 18.5- and/or MRC OX-12-positive B lymphocytes. The injection of LY117018 failed to elicit any changes in the number of cells expressing any of the phenotypes under investigation. The simultaneous injection of pertussigen, the major toxin responsible for the leukocytosis- and lymphocytosis-promoting activity of Bordetella pertussis, inhibited the estrogen-induced influx of eosinophils, macrophages (MRC OX-42-positive cells), and Ia (MRC OX-6)-positive cells but failed to prevent the influx of CD4 (W3/25) positive helper/inducer T lymphocytes. These results indicate that, in the immature rat, significant differences may exist in the susceptibility of various cell populations to the effects of estrogen, particularly with regard to uterine influx following estrogen stimulation. In addition, our observations suggest that either 1) the CD4-positive cells infiltrating the uterus following estrogen treatment may use a nonpertussigen-sensitive mechanism for chemotactic factor-receptor signal transduction or 2) a subpopulation of resident uterine cells can be induced to express the CD4 antigen following estrogen and/or estrogen plus pertussigen treatment.
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PMID:Immunohistochemical characterization of the estrogen-stimulated leukocyte influx in the immature rat uterus. 326 Jun 16

The responsiveness of adenylyl cyclase to beta-adrenergic receptor stimulation was investigated in membranes prepared from hypothalamus-preoptic area and cortex of ovariectomized female rats injected with oil vehicle or estradiol benzoate 24 or 48 h before death. Membranes from the hypothalamus-preoptic area of ovariectomized animals displayed a concentration-dependent stimulation of adenylyl cyclase when incubated with the beta-adrenergic receptor agonist, isoproterenol (10(-7)-10(-5) M). This response was suppressed in membranes from estrogen-treated animals. The effect of estrogen was observed 48 h, but not 24 h, after hormone administration. In addition, estrogen had no measurable effect on hypothalamic adenylyl cyclase activation by either GTP (10(-8)-10(-5) M) or forskolin (10(-8)-10(-6) M), on beta-adrenergic receptor density, or on antagonist binding affinity measured with the beta-adrenergic antagonist [125I]iodocyanopindolol. Analysis of isoproterenol displacement of iodocyanopindolol binding revealed that estrogen reduced agonist binding affinity in hypothalamus-preoptic area membranes. In membranes from ovariectomized controls, high affinity agonist binding to the beta-adrenergic receptor was apparent and was abolished by guanine nucleotides. However, membranes from estradiol-treated rats demonstrated only low affinity agonist binding that was unaffected by guanine nucleotides. Estradiol did not detectably alter concentrations of either cholera or pertussis toxin substrates in hypothalamus-preoptic area membranes. These data indicate that estrogen promotes a stable time-dependent desensitization of beta-adrenergic receptor activation of adenylyl cyclase in hypothalamus and preoptic area by uncoupling the receptor from the guanine nucleotide-binding protein, G8.
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PMID:Estrogen uncouples beta-adrenergic receptor from the stimulatory guanine nucleotide-binding protein in female rat hypothalamus. 824 9

Estrogen deficiency is associated with bone loss, and estrogen replacement is an effective treatment of this osteoporotic process. This study examines the early (5-120 s) effects of 17 beta-estradiol on the intracellular calcium and phospholipid metabolism in confluent female rat osteoblasts. The cytosolic free Ca2+ concentration ([Ca2+]i) was determined using fura-2/AM as Ca2+ probe. Cells were labeled with myo-[2-3H]inositol or [14C]arachidonic acid for inositol or lipid determination. Inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) production were determined by either mass measurement or anion-exchange chromatography or by thin-layer chromatography, respectively. 17 beta-Estradiol (1 pM to 1 nM) increased [Ca2+]i in a biphasic manner within 10 s via Ca2+ influx from the extracellular milieu, as shown by the effects of the calcium chelator EGTA and the Ca2+ channel blockers nifedipine and verapamil, and via Ca2+ mobilization from the endoplasmic reticulum (ER), as shown by the effects of thapsigargin. 17 beta-Estradiol (1 pM to 1 nM) induced a biphasic and concomitant increase in IP3 and DAG formation. Estradiol immobilized on bovine serum albumin (BSA) [E-(O-carboxymethyl)oxime BSA] and its derivative (O-carboxymethyl)oxime rapidly increased ([Ca2+]i, IP3, and DAG and were full agonists, although they were less potent than the free estradiol. They had the same action time course and acted via Ca2+ influx and Ca2+ mobilization from ER. Tamoxifen, a potent inhibitor of genomic steroid responses, did not block the rapid increase in Ca2+, IP3, and DAG induced by estradiol. Finally, inhibitor of phospholipase C (neomycin) and pertussis toxin abolished the effects of 17 beta-estradiol on IP3 and DAG formation. These results suggest that female rat osteoblasts bear non-genomic unconventional cell surface receptors for estradiol, belonging to the class of the membrane receptors coupled to a phospholipase C via a pertussis toxin-sensitive G protein.
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PMID:Cell signaling and estrogens in female rat osteoblasts: a possible involvement of unconventional nonnuclear receptors. 826 28

The effect of estradiol treatment of the human mammary carcinoma cell MCF-7 on the adenylyl cyclase system was examined. Treatment with 10 nM estradiol for 72 h increased the basal level of cAMP, and isoproterenol-, PGE2- or calcitonin-stimulated cAMP production. Estradiol also increased the response to cholera toxin but did not alter the response to forskolin. No significant change in growth rate was observed during the 72 h of estradiol treatment. In MCF-7 cell membranes the responsiveness to isoproterenol, PGE2, or cholera toxin was also enhanced by estradiol treatment. The cholera toxin-catalyzed ADP-ribosylation of Gs alpha in MCF-7 cell membranes was significantly increased by 72 h of treatment with estradiol. Consistent with this observation, the level of Gs alpha immunoreactivity was increased in the estradiol-treated cell membranes. On the other hand, pertussis toxin did not change the responsiveness to isoproterenol, PGE2 or calcitonin in either control or estradiol-treated cells. In addition, ADP-ribosylation with pertussis toxin also did not reveal any change in Gi. These results clearly indicate that Gs expression is under the control of estradiol, and that this effect may contribute to the increased sensitivity of hormone-stimulated adenylyl cyclase activities in MCF-7 cells.
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PMID:Estradiol up-regulates the stimulatory GTP-binding protein expression in the MCF-7 human mammary carcinoma cell line. 838 27

1. Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2. Oestradiol (10 nM-100 microM) relaxed arterial tissue pre-contracted by excess [K]o solution (30 mM) in a concentration-dependent manner. In Ca-free solution, histamine (10 microM) and caffeine (20 mM) each produced a phasic contraction, but oestradiol (10 microM) did not significantly affect their amplitude. 3. Oestradiol (< or = 100 microM) did not change the resting membrane potential of the artery whether in the presence or absence of TEA (10 mM). Action potentials observed in the presence of 10 mM TEA were abolished by oestradiol (100 microM). 4. Oestradiol (1 microM-100 microM) inhibited the voltage-dependent Ba current in a concentration-dependent manner. Oestradiol (100 microM) inhibited the Ba current observed in the presence of nicardipine (1 microM) more than that in the absence of nicardipine (to 31.0% vs 62.0% of control). 5. GTP gamma S (30 microM) in the pipette enhanced the inhibitory actions of oestradiol on the Ba current. On the other hand, with GDP beta S (1 mM) in the pipette, oestradiol failed to inhibit the Ba current. Pertussis toxin (PTX 3 micrograms ml-1) in the pipette totally prevented the inhibitory action of oestradiol on the Ba current. 6. Oestradiol (< or = 100 microM) had no significant effect on the outward K currents evoked by a membrane depolarization. 7. These results strongly suggest that oestradiol relaxes arterial tissue by inhibition of voltage-dependent Ca channels and that it inhibits both nicardipine-sensitive and -resistant Ca currents via a PTX-sensitive GTP-binding protein. The main target of oestradiol among the arterial Ca channels seems to be the nicardipine-resistant Ca channel, rather than the nicardipine-sensitive one.
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PMID:Oestradiol-induced relaxation of rabbit basilar artery by inhibition of voltage-dependent Ca channels through GTP-binding protein. 878 90

We investigated the effects of 17beta-estradiol, an estrogen, on [(3)H]norepinephrine ([(3)H]NE) secretion in PC12 cells. Pretreatment with 17beta-estradiol reduced 70 mM K(+)-induced [(3)H]NE secretion in a concentration-dependent manner with a half-maximal inhibitory concentration (IC(50)) of 2 +/- 1 microM. The 70 mM K(+)-induced cytosolic free Ca(2+) concentration ([Ca(2+)](i)) rise was also reduced when the cells were treated with 17beta-estradiol (IC(50) = 15 +/- 2 microM). Studies with voltage-sensitive calcium channel (VSCC) antagonists such as nifedipine and omega-conotoxin GVIA revealed that both L- and N-type VSCCs were affected by 17beta-estradiol treatment. The 17beta-estradiol effect was not changed by pretreatment of the cells with actinomycin D and cycloheximide for 5 h. In addition, treatment with pertussis or cholera toxin did not affect the inhibitory effect of 17beta-estradiol. 17beta-Estradiol also inhibited the ATP-induced [(3)H]NE secretion and [Ca(2+)](i) rise. In PC12 cells, the ATP-induced [Ca(2+)](i) rise is known to occur through P2X(2) receptors, the P2Y(2)-mediated phospholipase C (PLC) pathway, and VSCCs. 17beta-Estradiol pretreatment during complete inhibition of the PLC pathway and VSCCs inhibited the ATP-induced [Ca(2+)](i) rise. Our results suggest that 17beta-estradiol inhibits catecholamine secretion by inhibiting L- and N-type Ca(2+) channels and P2X(2) receptors in a nongenomic manner.
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PMID:Nongenomic inhibition of catecholamine secretion by 17beta-estradiol in PC12 cells. 1082 Feb 10

Estrogen rapidly activates the mitogen-activated protein kinases, Erk-1 and Erk-2, via an as yet unknown mechanism. Here, evidence is provided that estrogen-induced Erk-1/-2 activation occurs independently of known estrogen receptors, but requires the expression of the G protein-coupled receptor homolog, GPR30. We show that 17beta-estradiol activates Erk-1/-2 not only in MCF-7 cells, which express both estrogen receptor alpha (ER alpha) and ER beta, but also in SKBR3 breast cancer cells, which fail to express either receptor. Immunoblot analysis using GPR30 peptide antibodies showed that this estrogen response was associated with the presence of GPR30 protein in these cells. MDA-MB-231 breast cancer cells (ER alpha-, ER beta+) are GPR30 deficient and insensitive to Erk-1/-2 activation by 17beta-estradiol. Transfection of MDA-MB-231 cells with a GPR30 complementary DNA resulted in overexpression of GPR30 protein and conversion to an estrogen-responsive phenotype. In addition, GPR30-dependent Erk-1/-2 activation was triggered by ER antagonists, including ICI 182,780, yet not by 17alpha-estradiol or progesterone. Consistent with acting through a G protein-coupled receptor, estradiol signaling to Erk-1/-2 occurred via a Gbetagamma-dependent, pertussis toxin-sensitive pathway that required Src-related tyrosine kinase activity and tyrosine phosphorylation of tyrosine 317 of the Shc adapter protein. Reinforcing this idea, estradiol signaling to Erk-1/-2 was dependent upon trans-activation of the epidermal growth factor (EGF) receptor via release of heparan-bound EGF (HB-EGF). Estradiol signaling to Erk-1/-2 could be blocked by: 1) inhibiting EGF-receptor tyrosine kinase activity, 2) neutralizing HB-EGF with antibodies, or 3) down-modulating HB-EGF from the cell surface with the diphtheria toxin mutant, CRM-197. Our data imply that ER-negative breast tumors that continue to express GPR30 may use estrogen to drive growth factor-dependent cellular responses.
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PMID:Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. 1104 79

Estradiol (E(2))-signaling is widely considered to be exclusively mediated through the transcription-regulating intracellular estrogen receptor (ER) alpha and ERbeta. The aim of this study was to investigate transcription-independent E(2)-signaling in mouse IC-21 macrophages. E(2) and E(2)-BSA induce a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) of Fura-2 loaded IC-21 cells as examined by spectrofluorometry. These changes in [Ca(2+)](i) can be inhibited by pertussis toxin, but not by the ER-blockers tamoxifen and raloxifene. The E(2)-signaling initiated at the plasma membrane is mediated through neither ERalpha nor ERbeta, but rather through a novel G protein-coupled membrane E(2)-receptor as revealed by RT-PCR, flow cytometry, and confocal laser scanning microscopy. A special feature of this E(2)-receptor is its sequestration upon agonist stimulation. Sequestration depends on energy and temperature, and it proceeds through a clathrin- and caveolin-independent pathway.
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PMID:Estradiol signaling via sequestrable surface receptors. 1125 Sep 49

Estrogen causes rapid endothelial nitric oxide (NO) production because of the activation of plasma membrane-associated estrogen receptors (ER) coupled to endothelial NO synthase (eNOS). In the present study, we determined the role of G proteins in eNOS activation by estrogen. Estradiol-17beta (E(2), 10(-8) m) and acetylcholine (10(-5) m) caused comparable increases in NOS activity (15 min) in intact endothelial cells that were fully blocked by pertussis toxin (Ptox). In addition, exogenous guanosine 5'-O-(2- thiodiphosphate) inhibited E(2)-mediated eNOS stimulation in isolated endothelial plasma membranes, and Ptox prevented enzyme activation by E(2) in COS-7 cells expressing ERalpha and eNOS. Coimmunoprecipitation studies of plasma membranes from COS-7 cells transfected with ERalpha and specific Galpha proteins demonstrated E(2)-stimulated interaction between ERalpha and Galpha(i) but not between ERalpha and either Galpha(q) or Galpha(s); the observed ERalpha-Galpha(i) interaction was blocked by the ER antagonist ICI 182,780 and by Ptox. E(2)-stimulated ERalpha-Galpha(i) interaction was also demonstrable in endothelial cell plasma membranes. Cotransfection of Galpha(i) into COS-7 cells expressing ERalpha and eNOS yielded a 3-fold increase in E(2)-mediated eNOS stimulation, whereas cotransfection with a protein regulator of G protein signaling, RGS4, inhibited the E(2) response. These findings indicate that eNOS stimulation by E(2) requires plasma membrane ERalpha coupling to Galpha(i) and that activated Galpha(i) mediates the requisite downstream signaling events. Thus, novel G protein coupling enables a subpopulation of ERalpha to initiate signal transduction at the cell surface. Similar mechanisms may underly the nongenomic actions of other steroid hormones.
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PMID:Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). 1136 63

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