Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of tandospirone (TDS) on dissociated rat dorsal raphe neurones were investigated using the patch-clamp method. 2. Under current-clamp conditions, TDS hyperpolarized the cell membrane, resulting in the reduction of firing rates. 3. Under voltage-clamp conditions, TDS induced an inward rectifying K+ current in a concentration-dependent manner. 4. The TDS-induced K+ currents (I(TDS)) were mimicked by 8-OH-DPAT, a 5-HT1A agonist. The I(TDS) was blocked by spiperone, a 5-HT1A receptor antagonist, in a concentration-dependent manner. 5. N-Ethylmaleimide, an agent which uncouples between the receptor and the G-protein, irreversibly blocked the I(TDS). 6. In neurones perfused intracellularly with a pipette-solution containing GTP using the conventional whole-cell patch recording, the I(TDS) showed a gradual rundown. When the neurones were perfused with GTPgammaS, TDS activated the inwardly rectifying K+ current in an irreversible manner. 7. In the inside-out patch recording mode, TDS-activated single K+ channel currents (i(TDS)) which also showed an inward rectification. When the GDP in cytosolic side was completely replaced with GTP, the open probability of i(TDS) significantly increased. 8. These results indicate that the activation of 5-HT1A receptors by TDS directly opens the inward rectifying K+ channels via a G-protein mediated process.
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PMID:Tandospirone-induced K+ current in acutely dissociated rat dorsal raphe neurones. 969 74

Fast excitatory postsynaptic potentials (fEPSPs) occur in bursts in the myenteric plexus during evoked motor reflexes in the guinea-pig ileum in vitro. This study used electrophysiological methods to study fEPSPs during stimulus trains to mimic bursts of synaptic activity in vitro. The amplitude of fEPSPs or fast excitatory postsynaptic currents (EPSCs) declined (rundown) during stimulus trains at frequencies of 0.5, 5, 10 and 20 Hz. At 0.5 Hz, fEPSP or fEPSC amplitude declined by 50% after the first stimulus but remained constant for the remainder of the train. At 5, 10 and 20 Hz, synaptic responses ran down completely with time constants of 0.35, 0.21 and 0.11 s, respectively. Recovery from rundown occurred with a time constant of 7 s. Mecamylamine, a nicotinic cholinergic receptor antagonist, or PPADS, a P2X receptor antagonist, reduced fEPSP amplitude, but they had no effect on rundown. Responses caused by trains of ionophoretically applied ATP or ACh (to mimic fEPSPs) did not rundown. Blockade of presynaptic inhibitory muscarinic, adenosine A1, opioid, alpha2-adrenergic and 5-HT1A receptors or pertussis toxin (PTX) treatment did not alter rundown. Antidromic action potentials followed a 10-Hz stimulus train. Iberiotoxin (100 nM), a blocker of large conductance calcium activated K+ (BK) channels, did not alter rundown. These data suggest that synaptic rundown is not due to: (a) action potential failure; (b) nicotinic or P2X receptor desensitization; (c) presynaptic inhibition mediated by pertussis-toxin sensitive G-proteins, or (d) BK channel activation. Synaptic rundown is likely due to depletion of a readily releasable pool (RRP) of neurotransmitter.
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PMID:Dynamics of fast synaptic excitation during trains of stimulation in myenteric neurons of guinea-pig ileum. 1566 59