Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mRNA level of the type-1 angiotensin II receptor (AT1) was down-regulated by angiotensin II in cultured rat glomerular mesangial cells. The effect was maximum with 1 microM AII at 6 h, sensitive to cycloheximide, and specific to AT1 since this phenomenon was blocked by DuP753, an AT1 antagonist, but not by type-2 antagonist PD123319. Dibutyryl cAMP, forskolin, and cholera toxin also caused AT1 down-regulation. These effects were not altered by either the protein kinase A inhibitor H-8 or cycloheximide. Calcium ionophore A23187, pertussis toxin, protein kinase C inhibitor staurosporine, or prolonged incubation with phorbol ester were without effect. These results suggest that there are at least two pathways to down-regulate AT1 mRNA; one way is an angiotensin II-induced, protein kinase C-independent, and cycloheximide-sensitive pathway and the other is an angiotensin II-independent, cAMP-induced, and cycloheximide-insensitive pathway.
 ...
PMID:Two distinct pathways in the down-regulation of type-1 angiotension II receptor gene in rat glomerular mesangial cells. 159 49

Preincubation of human neutrophils with the human hormone granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibits the specific binding of leukotriene B4 ([3H]LTB4) but not the nonmetabolizable bioactive platelet-activating factor ([3H]C-PAF) to intact cells. This inhibition requires that the GM-CSF interacts with intact cells. The action of GM-CSF is not prevented by pertussis toxin. Moreover, the rise in calcium produced by LTB4 but not by PAF is also inhibited in human neutrophils pretreated with GM-CSF. Interestingly, neither the inhibitory action of GM-CSF on [3H]LTB4 binding or LTB4-induced calcium rise nor the potentiation of superoxide production by GM-CSF is reduced by inhibitors of arachidonic acid metabolism by the lipoxygenase pathway. In contrast, preincubation of human neutrophils with either the chemotactic factor formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) or the active phorbol ester, phorbol 12-myristate 13-acetate (PMA), inhibits the binding of both [3H]LTB4 and [3H]C-PAF to intact cells. The inhibitory actions of GM-CSF, PMA, and fMet-Leu-Phe require that they interact with the intact cells; their actions cannot be reproduced in plasma membrane preparations. The effects of both GM-CSF and fMet-Leu-Phe cannot be prevented by the protein kinase C inhibitor staurosporine. The mechanisms of fMet-Leu-Phe and GM-CSF actions are probably not mediated through the release of LTB4 by the cells. Interestingly, this new action, unlike other reported effects of GM-CSF, is not mediated through a pertussis toxin-sensitive G protein (Gi alpha 2). This indicates that not all GM-CSF receptors are coupled to Gi alpha 2.
 ...
PMID:Modulation of leukotriene B4 and platelet-activating factor binding to neutrophils. 165 24

Cultured retinal pigment epithelium cells prepared from post-mortem adult human eyes are shown to contain muscarinic receptors associated with phosphoinositide turnover. Carbachol at a concentration of 100 microM induced a four-fold increase in 3H-inositol phosphates (more than 76% is in the form of 3H-inositol-1-phosphate) accumulation within 45 min in cells prelabelled with 3H-myoinositol and exposed to 5 mM LiCl. The EC50 of carbachol was approx. 70 microM and the saturation concentration was about 1 mM. The carbachol-induced response was blocked by both atropine and pirenzepine, the former being most effective. Pre-exposure of cells to carbachol resulted in desensitization and a drastic reduction in the subsequent carbachol-induced stimulation of 3H-inositol phosphates. The carbachol response could be attenuated by the biologically active phorbol ester, 4 beta-phorbol 12-myristate 13-acetate, and this was nullified by the protein kinase C inhibitor, staurosporine. The biologically inactive phorbol ester, 4 alpha-phorbol 12,13 dideconoate, did not attenuate the carbachol-induced stimulation of 3H-inositol phosphates. Pertussis toxin failed to influence the carbachol receptor-mediated phosphoinositide turnover. These studies provide clear evidence for the occurrence of muscarinic receptors coupled to phosphoinositide hydrolysis on human retinal pigment epithelium cells.
 ...
PMID:Muscarinic acetylcholine receptor-mediated phosphoinositide turnover in cultured human retinal pigment epithelium cells. 165 4

Epidermal growth factor (EGF) inhibits Na transport in the cortical collecting ducts (CCD). To gain insight into the signal transduction of this effect, several potential mechanisms were examined in rabbit CCD perfused in vitro. Pretreatment with pertussis toxin, indomethacin, or the protein kinase C inhibitor H7 did not prevent the acute 34-50% decrease in lumen-to-bath 22Na flux (JNa) on exposure to peritubular EGF, indicating that the inhibition is not mediated by a Gi protein, prostaglandin E2 (PGE2), or protein kinase C. Inhibition of the basolateral Na-H exchanger was also without an effect. Lowering the bath Ca concentration from 1.2 to 0.11 mM did not prevent the inhibition of JNa by EGF (JNa decreased significantly by 38.7 +/- 6.9% and 29.1 +/- 5.3%, respectively); in contrast, reduction of the bath free Ca to 0.005 mM totally abolished the effect of EGF. The response to EGF was also assessed in the setting of chronic stimulation of Na transport; inhibition of JNa by EGF was still observed in CCD from remnant kidneys and in CCD from mineralocorticoid-treated rabbits. The results demonstrate that the inhibition of CCD Na transport by EGF is dependent on peritubular Ca. This suggests that the signal transduction involves Ca influx across the basolateral membrane and that increased cytosolic free Ca may be a common pathway for the counterregulatory control of Na reabsorption by several agonists.
 ...
PMID:Mechanism of sodium transport inhibition by epidermal growth factor in cortical collecting ducts. 165 25

The influence of noradrenaline and protein kinase C modulators on (+)-[3H]isradipine binding to voltage-dependent calcium channels has been studied in membranes of equine portal vein smooth muscle and intact strips isolated from rat portal vein. Specific (+)-[3H]isradipine binding to intact strips was increased by noradrenaline, a combination of aluminium and fluoride, and phorbol esters. The increase in isradipine binding induced by noradrenaline was inhibited by 1 microM prazosin while that induced by phorbol esters was inhibited by H7 (a protein kinase C inhibitor). In strips pretreated 6 h with 10 micrograms.ml-1 pertussis toxin, the noradrenaline-induced increase in isradipine binding was unchanged. In contrast, isradipine binding to membranes was unaffected by noradrenaline or GTP-gamma-S. Only phorbol esters had a stimulatory effect on isradipine binding when membranes were incubated in a medium containing 10 microM ATP and 5 mM Mg2+. Scatchard plot analysis reveals that the stimulation of isradipine binding by both noradrenaline and phorbol esters appears to result from a decrease in KD rather than an effect on the maximal binding capacity. Contractions evoked by noradrenaline were concentration-dependently depressed by isradipine. About 30% of the response was resistant to inhibition, while KCl-induced contractions were completely blocked. However, noradrenaline-induced contractions were more sensitive to isradipine inhibition than were KCl-induced contractions. These results suggest that activation of protein kinase C modulates isradipine binding to voltage-dependent Ca2+ channels independently of a separate modulation by membrane depolarization.
 ...
PMID:Modulation of [3H]dihydropyridine binding by activation of protein kinase C in vascular smooth muscle. 166 46

The influence of noradrenaline and protein kinase C modulators on (+)-[3H]isradipine binding to voltage-dependent calcium channels has been studied in membranes of equine portal vein smooth muscle and intact strips isolated from rat portal vein. Specific (+)-[3H]isradipine binding to intact strips was increased by noradrenaline and phorbol esters. The increase in isradipine binding induced by noradrenaline was inhibited by 1 microM prazosin and H7 (a protein kinase C inhibitor), while that induced by phorbol esters was only inhibited by H7. In strips pretreated with 10 micrograms/ml pertussis toxin for 6 h, the noradrenaline-induced increase in isradipine binding was unchanged. In contrast, isradipine binding to membranes was unaffected by noradrenaline or GTP-gamma-S. Only phorbol esters had a stimulatory effect on isradipine binding when membranes were incubated in a medium containing 10 microM ATP and 1 mM Mg2+. Scatchard plot analysis reveals that the stimulation of isradipine binding by both noradrenaline and phorbol esters appears to result from a decrease in KD rather than an effect on the maximal binding capacity. Contractions evoked by noradrenaline were concentration-dependently depressed by isradipine. About 30% of the response was resistant to inhibition, while KCl-induced contractions were completely blocked. However, noradrenaline-induced contractions were more sensitive to isradipine inhibition than were KCl-induced contractions. These results suggest that activation of protein kinase C modulates isradipine binding to voltage-dependent Ca2+ channels.
 ...
PMID:Pharmacology of Ca2+ channels in smooth muscle. 166 62

These studies provide evidence that binding of HDL3 to the HDL receptor stimulates translocation and efflux of intracellular cholesterol through mechanisms involving the activation of protein kinase C. This conclusion is supported by data demonstrating that HDL is able to increase cell diacylglycerol levels and activate protein kinase C. Sphingosine, a protein kinase C inhibitor, was able to inhibit HDL3-mediated cholesterol translocation and efflux, further suggesting a role for protein kinase C in HDL receptor-dependent cholesterol efflux. Inhibition of HDL-mediated diacylglycerol formation by pertussis toxin suggests the possible involvement of a G protein-activated phospholipase. Further studies are needed to understand how activation of protein kinase C promotes cholesterol translocation and to identify the target proteins for protein kinase C phosphorylation.
 ...
PMID:Role of the protein kinase C signaling pathway in high-density lipoprotein receptor-mediated efflux of intracellular cholesterol. 166 90

Exposure of 1321N1 human astrocytoma cells to fresh medium containing fetal bovine serum induced a marked increase in the subsequent ability of isoproterenol and forskolin to stimulate cAMP accumulation in intact cells, compared with cells exposed to fresh medium without serum. This "sensitization" of cAMP accumulation by serum was dose dependent, occurred rapidly, was maintained in the continuing presence of serum, and reversed rapidly upon removal of serum. Preliminary characterization of the sensitizing factor(s) in serum has been performed, but the factor(s) remain to be identified. Sensitization appeared to result from an increase in maximal response and not from changes in the potency of isoproterenol or forskolin. The protein kinase C inhibitor staurosporine inhibited serum-induced sensitization. Furthermore, down-regulation of protein kinase C almost completely eliminated the subsequent ability of serum to induce sensitization, indicating involvement of protein kinase C in the serum effect. Pretreatment of cells with pertussis toxin also markedly reduced subsequent sensitization induced by serum, suggesting involvement of a pertussis toxin-sensitive guanine nucleotide-binding protein in the pathway for serum-induced sensitization. The rate of cAMP degradation was not changed in sensitized cells, but some increase in adenylyl cyclase activity was retained in broken cell preparations from sensitized cells, suggesting increased synthesis of cAMP by adenylyl cyclase as the mechanism for sensitization.
 ...
PMID:Serum-induced sensitization of cyclic AMP accumulation in 1321N1 human astrocytoma cells. 170 72

Mastoparan, a tetradecapeptide component of wasp venom, is a potent activator of secretion in a variety of cell types, and has been shown to activate purified G-proteins reconstituted into phospholipid vesicles with a preferential activation of Gi over Gs (Higashijima, T., Uzu, S., Nakajima, T., and Ross, E. R. (1988) J. Biol. Chem. 263, 6491-6494). To identify the biochemical activities of mastoparan in a cellular system, we characterized the effects of mastoparan on signal transduction pathways in rat pulmonary alveolar type 2 epithelial cells, which synthesize and secrete pulmonary surfactant. Mastoparan inhibited adenylylcyclase activity in a manner that was dose-dependent (IC50 = 30 microM), but sensitive to neither guanine nucleotide nor pertussis toxin (PT). Mastoparan induced a PT-sensitive increase in cellular inositol trisphosphate and a rapid rise in cytosolic calcium released from intracellular stores; the time to onset of the calcium rise, but neither the rate nor the amplitude of the rise, were PT-sensitive. Mastoparan also caused a dose- (EC50 = 16 microM) and time-dependent activation of arachidonic acid release that was completely insensitive to pretreatment with PT. Secretion of pulmonary surfactant was increased by mastoparan approximately 8-fold over constitutive levels at 1 h with an EC50 = 20 microM, and mastoparan-stimulated secretion was partially sensitive to PT at late time points and to inhibitors of arachidonic acid metabolism, but not to the protein kinase C inhibitor H7. These findings are consistent with the activation of Gi proteins in type 2 cells by mastoparan, although the lack of predicted triphosphoguanine nucleotide and PT sensitivity for some activities indicates that mastoparan does not act in a manner strictly analogous to liganded receptors or that some activities are not mediated by activation of Gi. While mastoparan is a potent secretagogue in several cell types, its secretory activity appears to have only a limited dependence on the activation of Gi proteins in type 2 cells.
 ...
PMID:Mechanisms of mastoparan-stimulated surfactant secretion from isolated pulmonary alveolar type 2 cells. 184 93

The mechanism and site(s) of the defect responsible for desensitization to hormone stimulation of adenylyl cyclase (AC) vary with cell type. Plasma membrane preparations were assayed after treatment of primary cultured dog thyroid cells to determine the role of the TSH receptor, stimulatory and inhibitory guanine nucleotide binding proteins (Gs and Gi), and catalytic unit in AC desensitization. Exposure of cells to TSH or the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), caused time dependent decreases in TSH-stimulated AC and [125I]TSH binding with approximately 50% decreases seen after 18 h; Bt2cAMP was unable to reproduce the TSH effect. Whereas TSH treatment caused concomitant decreases (approximately 25%) in both cyclase activity and [125I]TSH binding after 2 h, TPA treatment decreased AC activity after 6 h and binding only after 18 h. The protein kinase C inhibitor, H-7, prevented TPA-induced but not TSH-induced effects on AC and hormone binding. Membrane AC activation by cholera toxin or forskolin was not altered by 18 h pretreatment of cells with TSH or TPA, indicating that these agents had no apparent effect on intrinsic functionality of either Gs or the catalytic unit. TSH or TPA pretreatment of cells reduced subsequent toxin-mediated AD[32P]-ribosylation of Gs and Gi in isolated membranes. However, the TSH- and TPA-induced decreases in AD[32P]-ribosylation and desensitization do not appear to be due to endogenous ribosylation of G proteins, since treatment of cells with pertussis toxin, for example, to endogenously ribosylate Gi, both increased TSH-stimulated AC activity and failed to affect the ability of TSH or TPA to desensitize. Thus, in this system, although specific hormone-induced AC desensitization and receptor down-regulation conform to several aspects of classic homologous processes, similar effects are also induced by a nonreceptor (phorbol ester) pathway; desensitization, however, can precede down-regulation, possibly due to receptor-Gs uncoupling.
 ...
PMID:Protein kinase C activation mimics but does not mediate thyrotropin-induced desensitization of adenylyl cyclase in cultured dog thyroid cells. 190 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>