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)

1. The effects of the selective thromboxane A2 (TXA2) receptor agonist I-BOP on neuronal excitability and synaptic transmission were studied in the CAl neurones of rat hippocampal slices by an intracellular recording technique. 2. Superfusion of I-BOP (0.5 microM) resulted in a biphasic change of the excitatory postsynaptic potential (e.p.s.p.), which was blocked by pretreatment with SQ 29548, a specific antagonist of TXA2 receptors. The inhibitory phase of I-BOP on the e.p.s.p. was accompanied by a decrease in neuronal membrane input resistance. 3. The sensitivity of postsynaptic neurones to glutamate receptor agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or N-methyl-D-aspartate (NMDA), was unchanged by I-BOP (0.5 microM) pretreatment. 4. Bath application of Ba2+ (0.5 mM) prevented both the I-BOP-induced reduction of the neuronal membrane input resistance and the blockade of e.p.s.p. induced by I-BOP. 5. Intracellular dialysis of the hippocampal CA1 neurones with GDP (10 mM) significantly attenuated the I-BOP inhibition of e.p.s.p. and membrane input resistance. Incubation of the slices with either pertussis toxin (PTX, 5 micrograms ml-1 for 12 h) or cholera toxin (CTX, 5 micrograms ml-1 for 12 h) did not affect the biphasic action of I-BOP on the e.p.s.p. or the reduction of membrane input resistance induced by I-BOP. 6. Pretreatment of the slices with the protein kinase C (PKC) inhibitor, NPC-15437 (20 microM), abolished the biphasic modulation by I-BOP (0.5 microM) of the e.p.s.p. Intracellular application of a specific PKC inhibitor, PKCI 19-36 (20 microM), completely inhibited the I-BOP reduction of e.p.s.p. The specific cyclic AMP-dependent protein kinase (PKA) inhibitor, Rp-cyclic adenosine 3',5'-monophosphate (Rp-cyclic AMPS, 25 microM), had no effect on the I-BOP action. 7. In this study we have demonstrated, for the first time, the existence of functional TXA2 receptors in the hippocampus which mediate the effects of a TXA2 agonist on neuronal excitability and synaptic transmission. Activation of the presynaptic TXA2 receptors may stimulate the release of glutamate. Conversely, activation of postsynaptic TXA2 receptors leads to inhibition of synaptic transmission resulting from a decrease in the membrane input resistance of the neurones. The pre- and postsynaptic actions of the TXA2 agonist are both mediated by PTX- and CTX-insensitive G-protein-coupled activation of PKC pathways.
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PMID:Thromboxane A2 agonist modulation of excitatory synaptic transmission in the rat hippocampal slice. 886 65

Whole cell voltage clamp recordings were used to investigate the effects of thromboxane A2 (TXA2) agonists on the voltage-dependent Ca2+ currents in rat hippocampal CA1 neurons. TXA2 agonists [1S-[1 alpha, 2 beta(5Z), 3 alpha(1E, 3S*)4 alpha ]]-7-[3-[3-hydroxy-4-(4'-iodophenoxy)-1-butenyl]-7-oxabicyclo [2,2,1]heptan-2-yl]-5-heptenoic acid (I-BOP) and U-46619, reversibly suppressed the whole cell Ca2+ currents in a concentration-dependent manner. The effect was blocked by specific TXA2 receptor antagonist, SQ-29548. I-BOP as well as U-46619 inhibited both omega-conotoxin GVIA (CgTx)-sensitive and nimodipine sensitive Ca2+ currents but had no effect on CgTx/nimodipine insensitive Ca2+ currents. The I-BOP and U-46619 inhibition of Ca2+ currents was blocked by internal dialysis of hippocampal neurons with specific protein kinase C (PKC) inhibitors, NPC-15437 and PKC inhibitor-(19-36). Pretreatment of hippocampal neurons with either 5 micrograms/ml pertussis toxin (PTX) or 5 micrograms/ml cholera toxin (CTX) did not significantly affect the suppression of the Ca2+ currents by I-BOP and U-46619. Dialyzing with 1 mM guanosine 5'-O-(3-thiotriphosphate) or 1 mM GDP significantly attenuated the I-BOP or U-46619 action. These results demonstrate that TXA2 agonists inhibit both CgTx- and nimodipine-sensitive Ca2+ currents but not CgTx/nimodipine-insensitive currents in rat hippocampal CA1 neurons via a PTX- and CTX-insensitive G protein-coupled activation of the PKC pathway.
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PMID:TXA2 agonists inhibit high-voltage-activated calcium channels in rat hippocampal CA1 neurons. 889 34

The postganglionic sympathetic nerves of the isolated rat stomach were electrically stimulated twice at 1 Hz for 1 min. Prostaglandin E(2) and ONO-AE-248 (16S-9-deoxy-9beta-chloro-15-deoxy-16-hyfroxy-17,17-trimethylene-19,20-didehydro prostaglandin F(2)) (an EP(3) receptor agonist) reduced the evoked noradrenaline release, while ONO-DI-004 (17S-2,5-ethano-6-oxo-17,20-dimethyl prostaglandin E(1)) (an EP(1) receptor agonist), ONO-AE1-259-01 (11,15-O-dimethyl prostaglandin E(2)) (an EP(2) receptor agonist) and ONO-AE1-329 [16-(3-methoxymethyl)phenyl-omega-tetranor-3,7-dithia prostaglandin E(1)] (an EP(4) receptor agonist) had no effect. U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha)) and I-BOP (7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2,2,1] hept-2-yl]-,[1S[1alpha,2alpha(Z),3beta(1E,3S)4alpha]]-5-heptenoic acid) (TP receptor agonists) also reduced the noradrenaline release and these inhibitory effects were abolished by SQ-29548 (7-[3-[[2-[(phenylamino) carbonyl] hydrazino]methyl]-7-oxabicyclo[2,2,1]hept-2-yl][1S(1alpha,2alpha(Z), 3alpha,4alpha]-5-heptenoic acid) (a TP receptor antagonist). The inhibitory effect of U-46619, but not ONO-AE-248, was abolished by pertussis toxin. These results suggest that the prostanoid EP(3) and TP receptors mediate the inhibition of gastric noradrenaline release; TP, but not EP(3), receptor-mediated inhibition is mediated by a pertussis toxin-sensitive mechanism in rats.
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PMID:Prostanoid EP3 and TP receptors-mediated inhibition of noradrenaline release from the isolated rat stomach. 1252 45