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)

In this study, we compared the localization of central 5-HT1 binding sites of rat and guinea pig. The 5-HT1B sites were absent in the guinea pig brain. Good correlations were found between species in the regional distribution of 5-HT1 sites labelled with [3H]5-HT (r = 0.73), 5-HT1A sites labelled with [3H]8-OH-DPAT (r = 0.87), and 5-HT1B versus 5-HT1D sites labelled with [3H]5-HT in the presence of ipsapirone and DOI (r = 0.76). Despite the overall similarities, species differences were observed in many brain regions. The CA1/CA2 fields of the hippocampus and the dorsal subiculum displayed significantly more 5-HT1A receptor binding in guinea pig than in rat. Conversely, the 5-HT1A binding in dorsolateral septum, cingulate cortex and laminae IV-V of the neocortex, was more pronounced in rat. Areas almost exclusively containing 5-HT1B or 5-HT1D sites, such as the ventral pallidum, globus pallidus and substantia nigra, expressed markedly more [3H]5-HT binding in rat as compared to guinea pig, while the opposite occurred in claustrum, dorsal endopiriform nucleus, lateral geniculate nucleus, and superficial grey layer of the superior colliculus. The implications of the species differences are illustrated by the binding of [3H]eltoprazine. The distribution of [3H]eltoprazine binding sites showed a good correlation with that of the 5-HT1B sites in rat (r = 0.89), and with that of the 5-HT1A sites in guinea pig (r = 0.97). The data give rise to the possibility that differences in the presence and distribution of 5-HT1 receptor sites are related to species differences in behavioural, neurochemical and physiological responses to drugs with 5-HT1 receptor affinity.
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PMID:Species differences in the distribution of central 5-HT1 binding sites: a comparative autoradiographic study between rat and guinea pig. 183 9

To date, there have been at least eight different receptors for the neurotransmitter serotonin (5-HT) identified in the central nervous system. These receptors fall into four pharmacological classes: 5-HT1, 5-HT2, 5-HT3 and 5-HT4. The 5-HT1 class has been shown to contain at least four pharmacologically distinct subtypes, 5-HT1A-D. Of these, cDNAs encoding the 5-HT1A and 5-HT1C receptors have been previously characterized. We now report the cloning and expression of a rat brain cDNA encoding another member of the 5-HT1 receptor family. Transient expression of this clone demonstrated high-affinity binding of [3H]5-HT with a pharmacological profile corresponding to that of the 5-HT1B subtype: 5-CT, 5-HT greater than propranolol greater than methysergide greater than rauwolscine greater than 8-OH-DPAT. In situ hybridization revealed expression of cognate mRNA within cells of the dorsal and median raphe nuclei, consistent with previous reports that the 5-HT1B receptor acts as an autoreceptor on 5-HT terminals in this species. mRNA expression was also detected in cells within the CA1 region of hippocampus, striatum, layer 4 of cortex and in the cerebellum, suggesting a previously unrecognized post-synaptic role for the 5-HT1B receptor.
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PMID:Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine1B receptor. 183 57

The effects of serotonin (5-HT), the 5-HT1A receptor subtype agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2 receptor subtype agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on electrophysiological responses in the dentate gyrus and area CA1 were examined in the in vitro hippocampal slice preparation. Superfusion of either serotonin or 8-OH-DPAT in the bath was found to inhibit population responses in a dose-dependent manner in both regions, with a greater effect in the CA1. The effects of 8-OH-DPAT in both regions were attenuated significantly by the serotonergic antagonist methysergide, as were the effects of 5-HT on the population spike in the CA1. The application of DOI did not produce statistically significant effects in either region. These findings support an inhibitory role for the 5-HT1A receptor in both area CA1 and the dentate gyrus.
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PMID:The effects of serotonergic compounds on evoked responses in the dentate gyrus and CA1 region of the hippocampal formation of the rat. 183 48

Pyramidal neurons in the rat CA1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA1 pyramidal neurons. The suppression of 5-HT responses was observed 1-4 hr after a brief (20-min) application of the steroids. Binding properties of the 5-HT1a receptor were not significantly affected by in vitro steroid application. Furthermore, responses to the GABAB agonist baclofen were not changed after treatment with MR ligands, implying that the K+ conductance to which both GABAB and 5-HT1a receptors are linked is also no target for the steroid action. The MR-mediated effect on 5-HT responsiveness potentially enhances cellular activity. Because activation of GRs was previously found to suppress norepinephrine-induced excitability in the same neurons, the data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events.
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PMID:Mineralocorticoid hormones suppress serotonin-induced hyperpolarization of rat hippocampal CA1 neurons. 186 15

The actions of 5-hydroxytryptamine (5-HT) and the 5-HT1A receptor ligand MDL 73005EF on neuronal activity in the CA1 region of rat hippocampal slices in vitro were recorded using intra- and extracellular recording techniques. 5-HT (1-30 microM) hyperpolarised the pyramidal neurones in a concentration-dependent manner and reduced membrane resistance and action potential after-hyperpolarisations (AHPs). MDL 73005EF (1-30 microM) had no clear effects on membrane potential, membrane resistance or AHPs. However, prior application of 3 microM MDL 73005EF to the slices for 10-60 min antagonised the hyperpolarisation induced by 30 microM 5-HT but not the reduction in spike AHP or the hyperpolarisation induced by the GABAB receptor agonist baclofen. MDL 73005EF and the 5-HT1A/2 receptor antagonist spiperone (both 3 microM) reduced the frequency and amplitude of spontaneous inhibitory (bicuculline-sensitive) postsynaptic potentials. Extracellular recordings of population action potentials revealed that MDL 73005EF did not prevent the induction or maintenance of hippocampal long-term potentiation or exhibit local anaesthetic properties. It is concluded that MDL 73005EF is an antagonist at 5-HT1A receptors on hippocampal CA1 pyramidal neurones.
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PMID:Electrophysiology of the 5-HT1A ligand MDL 73005EF in the rat hippocampal slice. 189 14

Electrophysiological studies, using chloral hydrate-anesthetized rats, were undertaken to determine whether hippocampal pyramidal neurons, receiving input from the medial septal nucleus, were affected by 5-hydroxytryptamine (5-HT) derived from the dorsal raphe nucleus. The pyramidal neurons in the CA1 region of the hippocampus were classified into short- and long-latency neurons, based on their response to stimulation of the medial septal nucleus. Microiontophoretically applied atropine inhibited the generation of spikes upon stimulation of the medial septal nucleus in short-latency neurons, but had no effect on long-latency neurons. In the short-latency neurons, the stimulation-induced spikes of the medial septal nucleus were inhibited by conditioning stimuli applied to the dorsal raphe nucleus and iontophoretic application of 5-HT and the 5-HT1A agonists, SM-3997 (3 a alpha,4 beta,7 beta,7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate) and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin). The conditioning effect of the dorsal raphe nucleus was antagonized by methysergide. However, in the long-latency neurons, the spikes elicited by stimulation of the medial septal nucleus were not affected by the conditioning stimulation of the dorsal raphe nucleus, or iontophoretically applied 5-HT. These results indicate that 5-HT, originating in the dorsal raphe nucleus inhibited hippocampal pyramidal neurons receiving cholinergic input from the medial septal nucleus, but not those receiving non-cholinergic input from the medial septal nucleus. The drug SM-3997 inhibited the activity of hippocampal pyramidal neurons, that receive excitatory cholinergic input from the medial septal nucleus by acting on 5-HT1A receptors.
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PMID:Inhibition of hippocampal CA1 neurons by 5-hydroxytryptamine, derived from the dorsal raphe nucleus and the 5-hydroxytryptamine1A agonist SM-3997. 197 Apr 26

Hippocampal pyramidal neurons of the CA1 region express 5-hydroxytryptamine (serotonin, 5-HT) receptors which, upon activation, elicit a slow membrane depolarization and a decrease in the calcium-activated afterhyperpolarization present in these cells. Previous electrophysiological studies have shown that this receptor(s) exhibits a pharmacological profile similar to that of the 5-HT1p, 5-HT3 and 5-HT4 subtypes. In the present study, intracellular recordings in rat brain slices were used in order to examine the effects of a variety of compounds that distinguish between these receptor subtypes. Administration of 5-HT in the presence of a 5-HT1A receptor antagonist elicited a depolarization and a concentration-dependent reduction in the amplitude of the afterhyperpolarization. These effects were mimicked by 5-methoxytryptamine and 5-carboxyamidotryptamine but not by 2-methyl-5-HT or phenylbiguanide. Administration of the benzamides BRL 24924, zacopride and cisapride blocked the responses to 5-HT with micromolar affinity although, in a small proportion of the cells tested, BRL 24924 was found to exhibit some agonist activity. This suggests that these compounds function as weak partial agonists in the rat hippocampus. These results establish clear differences between the 5-HT receptor(s) mediating the depolarization and reduction in the afterhyperpolarization in the hippocampus and the 5-HT3 and 5-HT1p receptors and suggest its classification in the 5-HT4 class. Thus, 5-HT4 receptors appear capable of mediating slow excitatory responses to 5-HT in the brain.
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PMID:5-Hydroxytryptamine4-like receptors mediate the slow excitatory response to serotonin in the rat hippocampus. 204 27

The activation of 5-hydroxytryptamine receptors exerts an inhibitory influence on neuronal activity in a way similar to the activation gamma-amino-n-butyric acid and adenosine A1 receptors. Therefore, we hypothesized that 5-HT1A-receptor agonists might exert a neuroprotective effect. We tested the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil. Ipsapirone protected 53% of pyramidal neurons (p less than 0.05) in the CA1 area of the hippocampus from ischemic damage at a dose of 3 mg/kg. Bay R 1531 showed a powerful neuroprotective effect with 100% preservation of neurons at a dose of 3 mg/kg (p less than 0.001) while gepirone and 8-OH-DPAT were ineffective. These findings suggest that 5-HT1A-receptor agonists might be effective tools for the therapy of cerebral ischemia. However, the varying results indicate that transient forebrain ischemia in the gerbil may not be the optimal model system to demonstrate clearly the neuroprotective activity of these compounds.
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PMID:Effects of 5-hydroxytryptamine1A-receptor agonists on hippocampal damage after transient forebrain ischemia in the Mongolian gerbil. 214 36

Administration of serotonin (5-hydroxytryptamine, 5-HT) to pyramidal cells of the CA1 region of the hippocampus results in a hyperpolarizing response which is followed by a rebound depolarization and a decrease in the calcium-activated afterhyperpolarization (AHP). While the hyperpolarizing response has been previously shown to be mediated by receptors of the 5-HT1A subtype, the identity of the receptor(s) involved in the depolarizing response and decrease of the AHP have not been identified. In the present study the effectiveness of a series of 5-HT receptor antagonists in blocking the membrane depolarization and reduction of the AHP was assessed. While a variety of 5-HT1 and 5-HT2 antagonists were found to be ineffective, the substituted benzamide BRL 24924 was found to be a potent and selective antagonist of the 5-HT-induced depolarization and decrease in the AHP in this region. This effect however appeared unrelated to the ability of this compound to block 5-HT3 receptors, as ICS 205-930 and MDL 72222 were markedly less efficacious in blocking these effects of 5-HT. Upon blockade of 5-HT1A receptors, 5-HT elicits a depolarization which is accompanied by a marked increase in excitability. These effects were also dose-dependently antagonized by BRL 24924. The present results thus suggest the presence in the CA1 region of the hippocampus of a novel 5-HT receptor at which BRL 24924 functions as a selective antagonist and which is capable of mediating slow excitatory responses in central neurons.
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PMID:Pharmacological and functional analysis of a novel serotonin receptor in the rat hippocampus. 222 19

The actions of serotonin (5-HT) and its putative agonists and antagonists were examined in vitro on hippocampal CA1 neurons using intracellular recordings, demonstrating that the cellular pharmacological effects can not necessarily be predicted from binding characteristics alone. The first response following 5-HT application was often a long-lasting (several minutes) hyperpolarization associated with decreased input resistance. Subsequent 5-HT applications caused only brief hyperpolarizations (30-120 s) and associated decreased input resistance, often followed by membrane depolarization. The post-spike train afterhyperpolarization (AHP) was prolonged for several minutes following the 5-HT induced hyperpolarization. 5-HT1 agonists (8-hydroxy-2-(di-n-propylamino)tetralin, 5-methoxytryptamine, MK-212) caused a prolonged hyperpolarization, decreased input resistance, and enhancement of the AHP. 5-HT applied following agonist application elicited only short-lasting hyperpolarizations. The 5-HT2 antagonists, cyproheptadine and mianserin, and a nonspecific 5-HT antagonist, methysergide, also caused a prolonged hyperpolarization with decreased input resistance. Spiperone, a nonspecific 5-HT antagonist, and ritanserin, a putative specific 5-HT2 receptor antagonist, depolarized CA1 neurons with little or no change in input resistance. The 5-HT-induced short-lasting hyperpolarization was not affected by drop application of 5-HT antagonists, except for methysergide, but perfusion of methysergide, ritanserin, and spiperone attenuated this response. The long-lasting 5-HT hyperpolarization might be mediated by 5-HT1A receptor activation, and the short-lasting hyperpolarization by another serotonergic receptor subtype.
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PMID:Serotonin agonist and antagonist actions in hippocampal CA1 neurons. 234 Apr 47


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