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)

Using iontophoretic techniques we observed that in vivo isapirone (TVX Q 7821), a selective ligand for the 5-HT1A binding site, at low ejection currents (5-30 nA) antagonised 5-HT and 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT)-induced suppression of hippocampal unit activity, with little effect on baseline firing rate itself. At higher ejection currents (20-100 nA) or following prolonged application, isapirone inhibited unit firing. Responses to GABA were unaffected by isapirone. These data demonstrate that isapirone is a 5-HT1A receptor antagonist with partial agonist properties on 5-HT sensitive neurones in the rat hippocampus.
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PMID:Isapirone is a partial agonist at 5-hydroxytryptamine 1A (5-HT1A) receptors in the rat hippocampus: electrophysiological evidence. 288 11

The propensity of SM-3997 to displace 3H-ligands was tested in vitro in a number of receptor-binding assays. SM-3997 possessed a high affinity towards 5-HT1A receptors, low affinity towards dopamine (D2) and 5-HT2 receptors, and no affinity towards benzodiazepine (BZ), GABA, 5-HT1B and adrenergic receptors. Moreover, SM-3997 facilitated neither 3H-flunitrazepam binding nor 3H-muscimol binding. These results suggest that the action of SM-3997 may be mediated via central 5-HT1A receptors but not the BZ-GABA receptor complex.
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PMID:Interaction of SM-3997 with serotonin receptors in rat brain. 289 33

The sustained administration of the 5-HT1A agonist gepirone (15 mg/kg/day, s.c.) in the rat produced an initial decrease of the firing activity of dorsal raphe 5-HT neurons which was followed by a progressive recovery to normal after 14 days of treatment. At this point in time, the effect of intravenous lysergic acid diethylamide (LSD) on the firing activity of 5-HT neurons was markedly reduced, whereas those of 8-hydroxy-2-N,N-propylamino-tetralin (8-OH-DPAT) and of gepirone were unchanged; however, the responsiveness of 5-HT neurons to direct microiontophoretic application of 5-HT, LSD, 8-OH-DPAT, and gepirone, but not of GABA, was reduced. The responsiveness of postsynaptic dorsal hippocampus pyramidal neurons to 5-HT, 8-OH-DPAT, and gepirone was not altered by the 14-day gepirone treatment. The effectiveness of the electrical stimulation of the ascending 5-HT pathway in reducing pyramidal neuron firing activity was not significantly modified in rats treated with gepirone for 14 days. Furthermore, this treatment did not alter the function of the terminal 5-HT autoreceptor. It is concluded that the progressive restoration of the firing activity of 5-HT neurons, due to a desensitization of the somatodendritic 5-HT autoreceptor, combined with the direct activation of normosensitive postsynaptic 5-HT1A receptor by gepirone, should result in an augmented tonic activation of postsynaptic 5-HT1A receptors. The progressive appearance of this phenomenon would be consistent with the time course of the clinical anxiolytic, and possibly antidepressant, effects of gepirone.
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PMID:Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. 290 33

We have synthesized 8-methoxy-2-(N-2'-chloropropyl, N-propyl) aminotetralin (8-methoxy-2'-chloro-PAT), an alkylating agent derived from the potent 5-HT agonist, 8-hydroxy-2-(N,N-dipropyl)-aminotetralin (PAT). As expected for an irreversible ligand, the blockade of 3H-PAT or 3H-5-HT binding to post-synaptic 5-HT1 (A and B) sites in rat hippocampal membranes pretreated with 8-methoxy-2'-chloro-PAT could not be prevented by extensive washing of membranes. Prior occupancy of 5-HT1 sites by 5-HT or PAT prevented any subsequent irreversible blockade by the alkylating agent. Similar irreversible blockade by 8-methoxy-2'-chloro-PAT was found on 3H-PAT binding to striatal membranes suggesting that presynaptic 5-HT binding sites (see Gozlan et al., Nature, Lond. 305, 140, 1983) were sensitive also to the alkylating agent. In contrast, the modifying agent N-ethylmaleimide (NEM) reduced markedly 3H-PAT binding to postsynaptic hippocampal 5-HT1 sites, but did not alter 3H-PAT binding to striatal presynaptic 5-HT sites. Although 8-methoxy-2'-chloro-PAT bound irreversibly to different classes of 5-HT binding sites (5-HT1A, 5-HT1B, presynaptic sites), it can be considered a selective alkylating agent, since it exerted no action on 3H-spiperone binding to 5-HT2 sites, 3H-muscimol binding to GABA sites, or 3H-flunitrazepam binding to benzodiazepine sites.
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PMID:Irreversible blockade of central 5-HT binding sites by 8-methoxy-2'-chloro-PAT. 315 2

We studied the effects of serotonin (5-HT) on intrinsic and synaptic responses of hippocampal CA1 cells. The effects were partially mimicked by the 5-HT1A receptor agonist, 8-OH-DPAT, and prevented by the 5-HT1A receptor antagonist, NAN-190. Polysynaptic fast and slow inhibitory postsynaptic potentials (IPSPs) were reduced in amplitude by 60-70% following application of both 5-HT and 8-OH-DPAT. Monosynaptic fast IPSPs were reduced by 60% and slow IPSPs by 90% following application of both drugs. Since there is a temporal overlap of fast and slow IPSPs, the reduction in fast IPSPs could have arisen indirectly from the larger effect of 5-HT on slow IPSPs. To overcome this problem we blocked the slow IPSPs with new, potent GABA-B antagonists, but still observed a similar reduction in the fast IPSP with 5-HT and 8-OH-DPAT. However, the reductions in the fast IPSPs could also have arisen from the 5-HT-induced total conductance increases. Using single-electrode voltage clamp and intracellular K+ channel blockers we still observed similar changes. 5-HT and 8-OH-DPAT had no effect upon GABA-A-mediated currents evoked by iontophoretic GABA application to the dendrites or the soma of CA1 pyramidal cells, Putative inhibitory internuerons were hyperpolarized by 5-HT and their evoked EPSPs strongly reduced by 5-HT and 8-OH-DPAT. Our data indicate that 5-HT modulates fast and slow synaptic inhibition of principal cells using presynaptic mechanisms involving the inhibition of inhibitory interneurons.
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PMID:Serotonin reduces inhibition via 5-HT1A receptors in area CA1 of rat hippocampal slices in vitro. 747 76

The 5-HT3 receptor blocking properties of YM060, YM114 (KAE-393), granisetron and ondansetron were examined in the vagus nerve and cerebral cortex of rats. 5-HT and 2-methyl-5-HT induced dose-dependent depolarizations of rat isolated vagus nerve with EC50 values of 2.53 (1.93-3.33) x 10(-6) and 4.03 (2.87-5.66) x 10(-6) M, respectively. YM060, YM114 and granisetron dose-dependently antagonized the depolarization of the rat vagus nerve induced by 5-HT, with decreases in the slope and maximal response at higher concentrations. Apparent pA2 values for these antagonists were 10.27 +/- 0.09, 10.12 +/- 0.16 and 9.44 +/- 0.40, respectively. Ondansetron produced a clear rightward shift of the concentration-response curve to 5-HT. The pA2 value was 8.63 (8.23-9.68). YM060 and YM114 at up to 10(-5) M produced no significant depression of the depolarizing responses to DMPP and GABA. YM060, YM114, granisetron and ondansetron displaced specific binding of [3H]GR65630 to rat cortical membranes with pKi values of 10.48 (10.41-10.57), 10.24 (10.18-10.28), 9.15 (9.02-9.28) and 8.70 (8.64-8.77), respectively. An excellent correlation (r = 0.97) was obtained between pA2 values in the vagus nerve and pKi values in the cerebral cortex. YM060, YM114, granisetron and ondansetron showed low affinities for 5-HT1A, 5-HT2 receptor, adrenergic alpha 1, alpha 2, dopamine D2, muscarinic M2, mu-opioid, benzodiazepine and histamine H1 receptors. These results support the possibility that the same type of 5-HT3 receptor occurs in rat vagus nerve and cerebral cortex.
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PMID:Comparative study of the affinities of the 5-HT3 receptor antagonists, YM060, YM114 (KAE-393), granisetron and ondansetron in rat vagus nerve and cerebral cortex. 756 99

This study investigated the possibility that overexpression of transforming growth factor alpha (TGF alpha) changes those neurotransmitter systems that have been associated with behaviors found to be altered in the transgenic TGF alpha CD-1 mice. The female TGF alpha mice showed elevated levels of norepinephrine (NE) in the hypothalamus and serotonin (5-HT) in the cortex and brain stem when compared with nontransgenic CD-1 females. The concentrations of monoamines were not altered in the male transgenic brain. The 5-hydroxyindoleacitic acid (5-HIAA)/5-HT ratio was significantly reduced in the brain stem of the male TGF alpha mice and frontal cortex in the female transgenics. The binding of the [3H]GBR 12935-labeled DA transporter was lower in the frontal cortex in the transgenic male TGF alpha mice than in the female TGF alpha mice. No gender difference in dopamine (DA) transporter binding was noted between the nontransgenic male and female mice. Serotonin and GABAA receptors were measured only in males. No differences in the number of 5-HT1A and 5-HT2 receptors were found in the cortex or hippocampus. Maximal GABA stimulation of [3H]flunitrazepam binding in the forebrain hemispheres and cerebellar binding of an imidazobenzodiazepine, [3H]Ro 15-4513, were not different between transgenic and nontransgenic male mice. However, forebrain [35S]TBPS binding in male TGF alpha mice was less affected by the blockade of the GABA agonist sites by the specific GABAA antagonists SR 95531 and bicuculline than the binding of the controls, suggesting either altered endogenous GABA concentrations or a change in receptor populations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in brain monoamines and GABAA receptors in transgenic mice overexpressing TGF alpha. 761 6

1. Whole-cell and intracellular recordings were made from neurons in slices of guinea-pig spinal trigeminal nucleus pars caudalis. 2. 5-Hydroxytryptamine (5-HT) hyperpolarized 70% of neurons by activating 5-HT1A receptors. The effect was mimicked by 5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronapthalene hydrobromide (8-OH-DPAT) and antagonized by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-butyl]-piperazine hydrobromide (NAN 190) and pindobind-5-HT1A. Nine per cent of the neurons were depolarized by 5-HT. 3. In about 20% of recordings, 5-HT also evoked repetitive inhibitory postsynaptic potentials that were mediated by glycine. 4. Noradrenaline (NA) hyperpolarized 71% of neurons. This effect was mediated by activation of alpha 2-adrenoceptors, since 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) also caused a hyperpolarization and idazoxan (1 microM) blocked the hyperpolarization to both NA and UK14304. Phenylephrine depolarized a subset of neurons and this depolarization was blocked by prazosin, suggesting an action mediated by activation of alpha 1-adrenoceptors. 5. NA also evoked repetitive GABAA-mediated inhibitory postsynaptic potentials in about 20% of recordings. The increase in synaptic activity was mimicked by phenylephrine and blocked by prazosin. 6. These results indicate that there are at least two mechanisms through which 5-HT and NA inhibit neurons: (i) in many cells both 5-HT and NA mediate a hyperpolarization through an increase of a potassium conductance; (ii) 5-HT and NA also activated GABA- and glycine-containing interneurons to cause IPSPs in separate groups of cells.
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PMID:Inhibition by 5-hydroxytryptamine and noradrenaline in substantia gelatinosa of guinea-pig spinal trigeminal nucleus. 765 66

1. The actions of 5-hydroxytryptamine (5-HT) on rat dentate gyrus neurones were measured with conventional intracellular recording techniques in brain slices maintained in vitro at 32 degrees C. 2. Bath application of 5-HT (0.3-100 microM) hyperpolarized the membrane potential and reduced the input resistance; these effects persisted in tetrodotoxin (1 microM) and were abolished by MDL 73,005EF, a 5-HT1A receptor antagonist. 3. Local application of 5-HT via a pressure pipette also elicited a hyperpolarization and a reduction in resistance, and evoked a transient 'burst' of spontaneous inhibitory postsynaptic potentials (IPSPs) which were blocked by tetrodotoxin or bicuculline. 4. The 'burst' of IPSPs was subject to desensitization. It was completely abolished in the presence of the 5-HT3 receptor antagonist dolasetron. 5. In some cells, a longer lasting increase in spontaneous IPSP frequency was observed during application of 5-HT; this effect was blocked by the 5-HT2 receptor antagonist MDL 100,907. 6. 5-HT (30 microM) shortened the decay time constants of the glutamatergic and GABAergic evoked EPSPs and IPSPs without changing their amplitudes. 7. It is concluded that 5-HT hyperpolarizes granule cells via postsynaptic 5-HT1A receptors and increases spontaneous GABA release from inhibitory interneurones via the activation of 5-HT3 receptors and/or 5-HT2 receptors.
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PMID:Transient and long-lasting actions of 5-HT on rat dentate gyrus neurones in vitro. 770 31

Hippocampal rhythmical slow activity (RSA) can be elicited by stimulation of the midbrain reticular formation. Buspirone, chlordiazepoxide and imipramine are all anxiolytic and have all been shown to decrease the frequency of RSA. All these compounds have been suggested to affect, directly or indirectly, 5-HT metabolism and function. The present experiments tested the possibility that buspirone, chlordiazepoxide and imipramine reduce RSA frequency via 5-HT1A autoreceptors. Rats received buspirone (10 mg/kg), chlordiazepoxide (5 mg/kg) and imipramine (30 mg/kg) after 5-HT depletion with p-chlorophenylalanine (pCPA, 100 mg/kg/day for 3 days or 350 mg/kg/day for 2 days) or after pretreatment with 5-HTP (40 mg/kg, to replete 5-HT) as well as pCPA. The frequency-reducing effects produced by buspirone and chlordiazepoxide were unchanged by either dose of pCPA, whereas the frequency-reducing effect of imipramine was completely eliminated by the high dose of pCPA. Pindolol, but not beta-blockers (a combination of metoprolol and ICI118,551), was able to block the effect of imipramine on RSA frequency. Pindolol has been reported to block the effects of buspirone but not chlordiazepoxide. These data suggest that: (1) buspirone obtains its frequency-reducing effects via pre- or post-synaptic 5-HT1A receptors rather than 5-HT1A autoreceptors; (2) chlordiazepoxide obtains its frequency-reducing effect via benzodiazepine receptors and GABA with no direct or indirect involvement of 5-HT systems; and (3) imipramine obtains its frequency-reducing effect by increasing the availability of 5-HT at 5-HT1A receptors which are not autoreceptors.
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PMID:The interaction of serotonin depletion with anxiolytics and antidepressants on reticular-elicited hippocampal RSA. 776 Sep 82


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