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• W2092281304 abstract "In the presence of NMDA receptor open‐channel blockers [Mg 2+ ; (+)‐5‐methyl‐10,11‐dihydro‐5 H ‐dibenzo[ a,d ]cyclohepten‐5,10‐imine maleate (MK‐801); 1‐amino‐3,5‐dimethyladamantane (memantine)] and TTX, high concentrations (30–100 μ M ) of either 5‐hydroxytryptamine (5‐HT) or α ‐methyl‐5‐hydroxytryptamine ( α ‐Me‐5‐HT) significantly potentiated NMDA‐induced depolarizations of frog spinal cord motoneurones. Potentiation was blocked by LY‐53,857 (10–30 μ M ), SB 206553 (10 μ M ), and SB 204741 (30 μ M ), but not by spiroxatrine (10 μ M ), WAY 100,635 (1–30 μ M ), ketanserin (10 μ M ), RS 102221 (10 μ M ), or RS 39604 (10–20 μ M ). Therefore, α ‐Me‐5‐HT's facilitatory effects appear to involve 5‐HT 2B receptors. These effects were G‐protein dependent as they were prevented by prior treatment with guanylyl‐5′‐imidodiphosphate (GMP‐PNP, 100 μ M ) and H‐Arg‐Pro‐Lys‐Pro‐Gln‐Gln‐D‐Trp‐Phe‐D‐Trp‐D‐Trp‐Met‐NH 2 (GP antagonist 2A, 3–6 μ M ), but not by pertussis toxin (PTX, 3–6 ng ml −1 , 48 h preincubation). This potentiation was not reduced by protein kinase C inhibition with staurosporine (2.0 μ M ), U73122 (10 μ M ) or N ‐(2‐aminoethyl)‐5‐isoquinolinesulfonamide HCl (H9) (77 μ M ) or by intracellular Ca 2+ depletion with thapsigargin (0.1 μ M ) (which inhibits Ca 2+ /ATPase). Exposure of the spinal cord to the L‐type Ca 2+ channel blockers nifedipine (10 μ M ), KN‐62 (5 μ M ) or gallopamil (100 μ M ) eliminated α ‐Me‐5‐HT's effects. The calmodulin antagonist N ‐(6‐aminohexyl)‐5‐chloro‐1‐naphtalenesulfonamide (W7) (100 μ M ) diminished the potentiation. However, the calcium/calmodulin‐dependent protein kinase II (CaM Kinase II) blocker KN‐93 (10 μ M ) did not block the 5‐HT enhancement of the NMDA responses. In summary, activation of 5‐HT 2B receptors by α ‐Me‐5‐HT facilitates NMDA‐depolarizations of frog motoneurones via a G‐protein, a rise in [Ca 2+ ] i from the entry of extracellular Ca 2+ through L‐type Ca 2+ channels, the binding of Ca 2+ to calmodulin and a lessening of the Mg 2+ ‐produced open‐channel block of the NMDA receptor. British Journal of Pharmacology (2004) 143 , 351–360. doi: 10.1038/sj.bjp.0705935" @default.
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• W2092281304 date "2004-10-01" @default.
• W2092281304 modified "2023-10-15" @default.
• W2092281304 title "Mechanisms intrinsic to 5-HT_2Breceptor-induced potentiation of NMDA receptor responses in frog motoneurones" @default.
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• W2092281304 doi "https://doi.org/10.1038/sj.bjp.0705935" @default.
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