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 aim of the present study was to test the effects of DAU 6215 (endo-N-(8-methyl-8-azabicyclo-[3.2.1]-octo-3-yl)-2,3-dihydro-2-ox o-1H- benzimidazole-1-carboxamide carboxamide hydrochloride), a newly synthesized, selective 5-hydroxytryptamine3 (5-HT3) antagonist, on the cell membrane properties and on characterized 5-HT-mediated responses of pyramidal neurones in the hippocampal CA1 region. 2. Administration of DAU 6215, even at concentrations several hundred fold its Ki, did not affect the cell membrane properties of pyramidal neurones, nor modify extracellularly recorded synaptic potentials, evoked by stimulating the Schaffer's collaterals. 3. Micromolar concentrations (15-30 microM) of 5-HT elicited several responses in pyramidal neurones that are mediated by distinct 5-HT receptor subtypes. DAU 6215 did not antagonize the 5-HT1A-induced membrane hyperpolarization and conductance increase, a response that was blocked by the selective 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalamido)butyl- piperazine). Similarly, DAU 6215 did not affect the membrane depolarization and decrease in amplitude of the afterhyperpolarization, elicited by the activation of putative 5-HT4 receptors. 4. 5-HT increased the frequency of spontaneous postsynaptic potentials (s.p.s.ps) recorded in pyramidal neurones loaded with chloride. In agreement with previous observations, most of the s.p.s.ps were reversed GABAergic events, produced by the activation of 5-HT3 receptors on interneurones, because they persisted in the presence of the glutamate NMDA and non NMDA antagonists, D-aminophosphonovaleric acid (APV; 50 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX; 25 microM), and were elicited by the selective 5-HT3 agonist, 2-methyl-5-HT (2-Me-5-HT, 50 microM). 5. The increase in frequency of s.p.s.ps induced by 5-HT was significantly antagonized by DAU 6215 in 70% of the cases, whereas the 5-HT3 antagonist always suppressed the effect of 2-Me-5-HT, at concentrations as low as 60 nM.6. The antagonistic effect of DAU 6215 was also tested on the 5-HT3-mediated block of induction of long-term potentiation (LTP), elicited by a primed burst (PB) stimulation. Extracellular recordings showed that low concentrations (60 nM) of DAU 6215 suppressed the inhibitory action of 5-HT onPB-induced LTP, without affecting the 5-HTlA-induced reduction in the amplitude of the population spike.7. These results provide evidence that DAU 6215 is an effective antagonist of the 5-HT3-mediated responses in the central nervous system and may offer a cellular correlate for the pharmacological effects of DAU 6215 as an anxiolytic and cognition enhancer.
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PMID:Effects of DAU 6215, a novel 5-hydroxytryptamine3 (5-HT3) antagonist on electrophysiological properties of the rat hippocampus. 807 90

Stimulation of glutamatergic NMDA receptor in adult rat hippocampal synaptoneurosomes induces statistically significant Ca(2+)-dependent liberation of arachidonic acid (AA) and nitric oxide (NO)-activated cGMP synthesis. NMDA acting for 5 min at 100 microM markedly increases, by approx. 25%, Ca(2+)-mediated AA release from phospholipids of hippocampal synaptoneurosomes. Prolonged stimulation of NMDA receptor up to 10 min has smaller stimulatory effect and enhances AA release by about 6%. Moreover, NMDA activates NO-dependent cGMP production by approx. 5 times more than the Ca2+ itself. Release of both these second messengers is completely blocked by the competitive NMDA antagonist, APV (100 microM). The NMDA-mediated cGMP elevation completely depends on NO action, and is abolished by the specific inhibitor of NO synthase, NG-nitro-L-arginine. Moreover, serotonin at 10 microM in the presence of 10 microM pargyline, potently decreases both Ca(2+)- and NMDA receptor-mediated AA and cGMP release in hippocampal synaptoneurosomes. The agonist of 5-HT1A receptor, buspirone, in a way similar to serotonin itself, counteracts the Ca(2+)- and also NMDA receptor-evoked AA release and cGMP accumulation. An antagonist of 5-HT1A receptor, NAN-190, eliminates the effect of serotonin and buspirone on AA and NO/cGMP liberation. An antagonist of serotonergic 5-HT2 receptor, ketanserin, has no effect on the Ca2+ and serotonin action. These results indicate that serotonin, through 5-HT1A receptor, potently antagonizes the action of excitatory amino acid for AA release and NO/cGMP synthesis in the adult rat hippocampus. In conclusion, the interaction of serotonin with the glutamatergic system in the hippocampus may play an important role in the modulation of a signal transduction pathway, and by this molecular mechanism serotonin may exert a neuroprotective effect on hippocampal neurons.
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PMID:Activation of serotonergic 5-HT1A receptor reduces Ca(2+)- and glutamatergic receptor-evoked arachidonic acid and No/cGMP release in adult hippocampus. 874 Apr 52