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

The signal transduction of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), cyclooxygenase products of arachidonic acid, was investigated in smooth muscle preparations and 1321N1 human astrocytoma cells. While PGE2 has been known to stimulate (via EP2 receptor) or inhibit (via EP3 receptor) adenylate cyclase, PGE2 activated phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLase C) in non-vascular smooth muscles (via EP1 receptor), resulting in accumulations of inositol trisphosphate (IP3) and diacylglycerol to elicit intracellular Ca2+ mobilization. On the other hand, STA2, a TXA2 receptor analogue, also accumulated IP3 in human astrocytoma cells. [3H]SQ 29548, a TXA2 receptor antagonist, specifically bound to astrocytoma membranes. TXA2-receptor antagonists (ONO NT-126, S-145, SQ29548 and ONO3708) concentration-dependently inhibited PIP2-specific PLase C activation by STA2, and they also inhibited [3H]SQ 29548 binding in human astrocytoma cells. The Ki value of each antagonist in PIP2-specific PLase C inhibition was similar to that in [3H]SQ29548 binding inhibition. In membrane preparations, STA2 activated PIP2-specific PLase C in the presence of GTP gamma S. Pertussis toxin (IAP) did not affect STA2-induced PLase C activation. The results suggest that stimulation of TXA2 receptors activates PIP2-specific PLase C via an IAP-insensitive G-protein.
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PMID:[Signal transduction of prostaglandin E2 and thromboxane A2]. 131 76

In human D384 astrocytoma cells, cyclic AMP accumulation can be conveniently studied after labelling of the adenosine triphosphate pool (15 fmol cell-1) with [3H]adenine. In this study, adenosine had a biphasic effect on cyclic AMP accumulation, which was scarcely altered by blocking adenosine uptake and metabolism. Low concentrations of adenosine led to an inhibition of cyclic AMP accumulation, and higher concentrations led to stimulation. No effect of adenosine on cyclic AMP was observed unless phosphodiesterase was inhibited by rolipram. The A1 receptor antagonist DPCPX attenuated the inhibitory phase of adenosine response, and enhanced the cyclic AMP accumulation induced by adenosine analogues. The cyclic AMP accumulation was stimulated by NECA greater than ADO greater than CGS 21680 greater than CV 1808 greater than CPA greater than or equal to CHA, indicating mediation by A2 receptors. The stimulatory effect of NECA was much more effectively blocked by the combined A1 and A2 receptor antagonist CGS 15943 (KB 4 nmol l-1) than by the A1 antagonist DPCPX (KB 110 nmol l-1). Treatment of the cells with pertussis toxin (0.2 microgram ml-1 for 2.5 h) potentiated the cyclic AMP response to adenosine analogues significantly. The cyclic AMP response to NECA was enhanced by the protein kinase C activator phorbol dibutyrate even after pertussis toxin treatment. By contrast, nanomolar concentrations of bradykinin, which increases Ca(2+)-levels and protein kinase C activity in D384 cells, reduced NECA-induced cyclic AMP accumulation in control and pertussis toxin-treated cells. Thus, D384 cells possess both A1 and A2 adenosine receptors influencing cyclic AMP in opposite directions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine receptor-induced cAMP changes in D384 astrocytoma cells and the effect of bradykinin thereon. 131 54

The effect of adenosine on phosphoinositide hydrolysis was examined in 1321N1 human astrocytoma cells. Adenosine, L-N6-phenylisopropyladenosine (L-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA) inhibited histamine-stimulated accumulation of inositol phosphates in a concentration-dependent manner. The potency order of adenosine analogues for inhibition of inositol phosphate accumulation was L-PIA greater than adenosine greater than NECA, a finding indicating that A1-class adenosine receptors are involved in the inhibition. The reduction in inositol phosphate accumulation by L-PIA was blocked by an adenosine receptor antagonist, 8-phenyltheophylline. Stimulation of A1-class adenosine receptors inhibited isoproterenol-stimulated cyclic AMP accumulation as well as histamine-induced inositol phosphate accumulation. Both inhibitory effects were blocked by pretreatment of the cells with pertussis toxin [islet-activating protein (IAP)]. L-PIA also inhibited guanosine 5'-(gamma-thio)triphosphate (GTP gamma S)-stimulated accumulation of inositol phosphates in membrane preparations, and 8-phenyl-theophylline antagonized the inhibition. L-PIA could not inhibit GTP gamma S-induced accumulation of inositol phosphates in IAP-treated membranes. Gi/Go, purified from rabbit brain, inhibited GTP gamma S-stimulated accumulation of inositol phosphates in a concentration-dependent manner in membrane preparations. These results suggest that stimulation of A1-class adenosine receptors interacts with the IAP-sensitive G protein(s), resulting in the inhibitions of phospholipase C as well as adenylate cyclase in human astrocytoma cells.
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PMID:Adenosine inhibits histamine-induced phosphoinositide hydrolysis mediated via pertussis toxin-sensitive G protein in human astrocytoma cells. 165 Mar 98

Pretreatment of 1321N1 human astrocytoma cells with phorbol 12-myristate-13-acetate or other activators of protein kinase C led to 2.5- to 5-fold increases (sensitization) in subsequent stimulation by forskolin of intracellular cyclic AMP accumulation. These compounds caused much smaller or no increases in receptor-mediated stimulation of cyclic AMP accumulation induced by isoproterenol and by prostaglandin E1. Carbachol and histamine, agonists acting at receptors coupled to polyphosphoinositide turnover in these cells, induced less sensitization of subsequent stimulation by forskolin but greater sensitization of stimulation by isoproterenol and by prostaglandin E1. The specificities of various analogs of phorbol 12-myristate-13-acetate, for induction of sensitization of forskolin stimulation were consistent with involvement of protein kinase C. The effects of protein kinase inhibitors and of down-regulation of protein kinase C activity also indicated involvement of protein kinase C in sensitization of forskolin stimulation, although additional mechanisms are likely to be involved in sensitization of isoproterenol stimulation. Neither pertussis toxin pretreatment nor inclusion of isobutylmethylxanthine during assays of cyclic AMP accumulation were able to prevent or mimic these sensitization phenomena, suggesting that the primary site of modification responsible for sensitization is neither the inhibitory guanine nucleotide-binding protein nor cyclic AMP phosphodiesterase. Sensitization was only observed in assays with intact cells. These results, together with those from our previous study describing protein kinase C-mediated desensitization of broken cell adenylate cyclase activity, indicate that activation of protein kinase C leads to multiple changes in the receptor-stimulated adenylate cyclase signal transduction pathway of these cells.
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PMID:Protein kinase C activators sensitize cyclic AMP accumulation by intact 1321N1 human astrocytoma cells. 168 54

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.
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PMID:Serum-induced sensitization of cyclic AMP accumulation in 1321N1 human astrocytoma cells. 170 72

Stimulation of thromboxane A2 (TXA2) receptors in human astrocytoma cells (1321N1) results in activation of phospholipase C via a pertussis toxin-insensitive G-protein. In the present study, the potency of a new TXA2 receptor antagonist, ONO NT-126, was examined with regard to receptor binding and phosphoinositide hydrolysis in human astrocytoma cells and was compared to that of the other known TXA2 antagonists. [3H]SQ29548 binding to membranes was inhibited by ONO NT-126 and the other TXA2 antagonists with Ki values (nM) of 0.09, 2.18, 8.35 and 25.9 for ONO NT-126, S-145, SQ29548 and ONO3708, respectively. STA2 and U46619, TXA2 receptor agonists, also inhibited [3H]SQ29548 binding with Ki (nM) of 25.1 and 233.5, respectively. STA2 and U46619 stimulated phosphoinositide hydrolysis in a concentration-dependent manner with EC50 values of 43.6 nM for STA2 and 1.2 microM for U46619, respectively. STA2 (1 microM)-induced phosphoinositide hydrolysis was also inhibited by TXA2 antagonists. The Ki values of TXA2 antagonists for the inhibition of phosphoinositide hydrolysis (nM) were 0.10 for ONO NT-126, 3.31 for S-145, 8.31 for SQ29548 and 19.49 for ONO3708 all of which were similar to those for receptor binding. The results indicate that ONO NT-126 is a potent and selective antagonist of TXA2 receptors in human astrocytoma cells.
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PMID:ONO NT-126 is a potent and selective thromboxane A2 antagonist in human astrocytoma cells. 196 27

Mastoparan inhibited [3H]inositol phosphate accumulation induced by carbachol as well as cyclic AMP accumulation induced by isoproterenol in 1321N1 human astrocytoma cells. Mastoparan inhibited GTP gamma S-induced, but not Ca2(+)-induced, [3H]inositol phosphate accumulation in membrane preparations with an IC50 of approximately 10 microM. The inhibitory effect of mastoparan on carbachol-induced [3H]inositol phosphate accumulation was resistant to pertussis toxin (IAP) treatment in intact cells. These results suggest that mastoparan inhibits phospholipase C in human astrocytoma cells via a GTP binding protein, which is not a substrate for IAP.
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PMID:Mastoparan inhibits phosphoinositide hydrolysis via pertussis toxin-insensitive [corrected] G-protein in human astrocytoma cells. 215 79

A human astrocytoma cell line, U373, and its subclones showed a high proliferative response to IL1 alpha or IL1 beta with concomitant IL6 production and IL6 mRNA accumulation. IL1 itself raised neither the cAMP level nor the intracellular Ca2+ level nor did it induce phosphatidylinositol (PI) breakdown. Chorela toxin (CT) and pertussis toxin (PT)-pretreatment markedly inhibited IL1-induced proliferation, while CT enhanced IL1-induced IL6 mRNA expression significantly. Drugs raising cellular cAMP level or cAMP analogues augmented IL1-mediated IL6 mRNA expression but much less. Although cAMP is not directly involved in the IL1 action, cAMP thus has a modulatory effect on IL1-mediated IL6 gene activation.
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PMID:IL1 induces proliferation and IL6 mRNA expression in a human astrocytoma cell line: positive and negative modulation by chorela toxin and cAMP. 215 29

The H1-histamine receptor antagonist [3H]mepyramine bound with high affinity (Kd = 3-5 nM) to membranes derived from 1321N1 human astrocytoma cells. The H1-receptor antagonists triprolidine and diphenhydramine inhibited [3H]mepyramine binding with Kj values of 1-5 nM, whereas the Kj of the H2-histamine receptor antagonist cimetidine was greater than 100 microM. Histamine also inhibited [3H]mepyramine binding to 1321N1 cell membranes, and the histamine inhibition curve was shifted to the right and steepened in the presence of 1 microM guanosine 5'-O-(3-thiotriphosphate). Treatment of 1321N1 cells with pertussis toxin had no effect on the capacity of histamine to inhibit [3H]mepyramine binding either in the absence or presence of guanosine 5'-O-(3-thiotriphosphate). Therefore, agonist-occupied histamine receptors in these cells apparently interact with a guanine nucleotide regulatory protein that is not the inhibitory guanine nucleotide regulatory protein of adenylate cyclase. Although adenylate cyclase activity was not affected by histamine in a cell-free preparation, incubation of 1321N1 cells with histamine resulted in an attenuation of cyclic AMP accumulation. Analysis of cyclic AMP degradation in the presence of histamine indicated that the effects of histamine on cyclic AMP accumulation are mediated through activation of phosphodiesterase. This idea was supported by the fact that the phosphodiesterase inhibitor 1-isobutyl 3-methylxanthine blocked attenuation of cyclic AMP accumulation by histamine in a noncompetitive manner. Histamine also markedly increased phosphoinositide breakdown and 45Ca2+ efflux in 1321N1 cells. These histamine-induced effects apparently are mediated through H1-receptors, since triprolidine, but not cimetidine, potently inhibited histamine action. As for histamine interaction with its receptor, pertussis toxin had no effect on histamine-induced phosphoinositide breakdown, 45Ca2+ efflux, or attenuation of cyclic AMP accumulation. Taken together, these data indicate that 1321N1 human astrocytoma cells are a useful model system for the study of H1-histamine receptors and the biochemical responses mediated through these receptors.
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PMID:H1-histamine receptors on human astrocytoma cells. 241 44

An adenosine receptor has been characterized to unambiguously demonstrate that the inhibitory guanine nucleotide regulatory protein, Gi, of 1321N1 human astrocytoma cells is fully capable of functionally coupling to adenylate cyclase. Adenosine receptor agonists attenuated cyclic AMP accumulation by 35 to 75% with the order of potency of N6(R-phenylisopropyl)-adenosine greater than adenosine = 2-chloroadenosine greater than N6-methyladenosine = N6-benzyladenosine. 3-Isobutyl-1-methylxanthine competitively antagonized the effect of adenosine receptor agonists. Adenylate cyclase activity measured in cell-free preparations from 1321N1 cells was inhibited by N6(R-phenylisopropyl)-adenosine. Pretreatment of 1321N1 cells with pertussis toxin blocked both adenosine receptor-mediated inhibition of adenylate cyclase activity and attenuation of cyclic AMP accumulation. In contrast to the effects on responses to adenosine receptor agonists, 3-isobutyl-1-methylxanthine noncompetitively antagonized muscarinic receptor-mediated attenuation of cyclic AMP accumulation and pertussis toxin had no effect. These data are consistent with the ideas that Gi is fully functional in 1321N1 cells and links inhibitory adenosine receptors to adenylate cyclase, and that the muscarinic receptor of these cells couples to the phosphoinositide response system, but is incapable of functionally coupling through Gi to inhibit adenylate cyclase.
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PMID:Adenosine and muscarinic cholinergic receptors attenuate cyclic AMP accumulation by different mechanisms in 1321N1 astrocytoma cells. 242 Sep 67


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