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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-HT autoreceptors involved in the regulation of 5-HT release in the guinea pig dorsal raphe nucleus have been studied in comparison with those in the hypothalamus. In vitro release was measured in slices of raphe and hypothalamus prelabelled with [3H]5-HT, superfused with Krebs solution and depolarized electrically. The non-selective 5-HT receptor agonist, 5-carboxamidotryptamine (5-CT) (0.1-10 nM for raphe: 1-100 nM for hypothalamus) and antagonist, methiothepin (10-1000nM), decreased and increased, respectively, the release of [3H]5-HT evoked by electrical stimulation in either of these regions when given alone. The selective 5-HT1B/D receptor antagonist, GR127935 (100-1000 nM), and the 5-HT1D receptor antagonist, ketanserin (300-1000 nM), had no significant effect on this release in either of these regions. Methiothepin and GR127935 (100-1000 nM) shifted to the right the concentration-effect curve of 5-CT in both the raphe and the hypothalamus. At 300 nM, ketanserin shifted to the right the concentration-effect curve of 5-CT in the raphe but did not modify the 5-CT curve in the hypothalamus. In microdialysis experiments ketanserin, applied locally at 10 microM, increased the extracellular levels of 5-HT in the dorsal raphe nucleus of the freely moving guinea pig, whereas 5-HT levels were unchanged in the hypothalamus. Ketanserin at 1 microM did not affect the decrease in 5-HT output induced by the selective 5-HT1B/D receptor agonist, naratriptan (used at 10 microM in raphe and 0.1 microM in hypothalamus), in the raphe or the hypothalamus. In the raphe, WAY100635, a 5-HT1A receptor antagonist, at 1 microM, did not prevent naratriptan (10 microM) from reducing the extracellular levels of 5-HT. These results suggest that, in the conditions used in this study, the release of 5-HT in the dorsal raphe nucleus is possibly modulated in part by 5-HT1B receptors but essentially the control is through 5-HT receptors whose subtype is still to be determined. In the hypothalamus, however, it is clear that only 5-HT1B receptors are involved in the modulation of 5-HT neurotransmission.
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PMID:5-HT autoreceptors in the regulation of 5-HT release from guinea pig raphe nucleus and hypothalamus. 951 43

Three rat lines were selectively bred for high (HDS), random (RDS), or low (LDS) hypothermic responses to the specific 5-HT1A receptor agonist 8-OH-DPAT. Forty-five minutes after 8-OH-DPAT administration (0.5 mg/kg), body temperatures dropped 3-5 degrees C in HDS rats, yet this dose produced only about 1.2 degrees C and 0.7 degree C drops in RDS and LDS rats, respectively. To investigate the relationship of body temperature of 5-HT1A receptor binding sites, autoradiographic analyses of [3H]8-OH-DPAT binding to 5-HT1A receptors in brains of these rats were conducted. Significant differences in binding were found in specific limbic cortical projection sites, with the HDS line having the greatest density of sites. Body temperature responses correlated significantly with [3H]8-OH-DPAT receptor binding in only a few areas of frontal cortex. Binding in many other brain regions, including the anterior and posterior hypothalami (regions long associated with body temperature regulation) and the raphe showed no significant differences among the lines. [3H]Ketanserin binding to cortical 5-HT2 receptors did not differ among the lines, except in the cingulate and superficial frontal cortices where HDS exhibited higher binding. These data suggest that differences in 5-HT1A receptor number may contribute to the exaggerated hypothermic response to 8-OH-DPAT in HDS rats. These studies also suggest that genetic regulation of receptor density may be brain region specific which should encourage future studies of the mechanisms of 5-HT1A receptor activity in brain and the action of drugs affecting this receptor.
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PMID:Brain 5-HT1A receptor autoradiography and hypothermic responses in rats bred for differences in 8-OH-DPAT sensitivity. 951 43

Dysfunction of brain 5-hydroxytryptaminergic systems has been associated with several neurological and psychiatric diseases which may have a viral aetiology. The effect of Semliki Forest virus (SFV) on 5-hydroxytryptamine (5-HT1A and 5-HT2A) receptors in mouse brain has been assessed by membrane homogenate binding and autoradiography. Adult mice were injected with saline or virus and brains removed 2, 6, 14, 22 and 35 days after infection. 5-HT1A and 5-HT2A receptors were characterised by saturation studies using [3H] 8-OH-DPAT and [3H] Ketanserin respectively. SFV infection increased 5-HT1A receptor numbers by up to 80% in the cortex on days 6, 14, and 22 but had no effect on Bmax in the midbrain, pons/medulla and the hypothalamus. SFV infection did not affect 5-HT2A receptor number in any of the brain regions studied and the affinity (Kd) of either ligand for 5-HT1A or 5-HT2A receptors was unaffected. Autoradiographic mapping of 5-HT1A receptors in SFV-infected brain showed substantially higher binding in nucleus accumbens, tenia tecta, septohippocampal nucleus, septum, medial and basolateral amygdaloid nucleus, anterioventral preoptic nucleus, hippocampus, interpeduncular nucleus, frontal, lateral orbital, and entorhinal cortex and claustrum on days 6 and 14. Elevated binding persisted in tenia tecta, frontal, lateral orbital, entorhinal cortex, and hippocampal formation to day 22. Autoradiography of 5-HT2A receptors using [3H] Ketanserin showed no difference in the binding in SFV-infected brains. A decrease in plasma corticosterone levels in SFV-infected mice was observed on post infection days 6 and 22. These results show SFV infection induces a regionally selective upregulation of 5-HT1A but not 5-HT2A receptors.
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PMID:Regional changes in 5-HT1A but not in 5-HT2A receptors in mouse brain after Semliki Forest virus infection: radioligand binding and autoradiographic studies. 1006 2

Attempts were made to further analyze the role of 5-HT1A receptors in consolidation of learning by evaluating the role of these receptors in cognitively normal and impaired animals. The effects of post-training administration of 8-OH-DPAT and 5-HT1A receptor antagonists, WAY 100135, WAY 100635, and S-UH-301, plus the cholinergic and glutamatergic antagonists, scopolamine and dizolcipine, respectively, were determined using an autoshaping learning task. The results showed that 8-OH-DPAT increased the number of conditioned responses, whereas WAY100135, WAY100635, and S-UH-301, and the 5-HT depleter, p-chloroamphetamine (PCA), had no effect. PCA did not change the silent properties of the 5-HT1A receptor antagonists. PCA, WAY100635, and S-UH-301, but not GR127935 (a 5-HT1B/1D-receptor antagonist) or MDL100907 (a 5-HT2A receptor antagonist), reversed the effect to 8-OH-DPAT. Ketanserin (a 5-HT2A/2C receptor antagonist) and ondansetron (a 5-HT3 receptor antagonist), at a dose that increased the conditioned responses by itself, reversed the effect of 8-OH-DPAT. Moreover, 8-OH-DPAT or S-UH-301 reversed the learning deficit induced by scopolamine and dizocilpine whereas WAY100635 reversed the effect of scopolamine only. These data confirm a role for presynaptic 5-HT1A receptors during the consolidation of learning and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals.
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PMID:5-HT1A receptors modulate the consolidation of learning in normal and cognitively impaired rats. 1008 40

5-Hydroxytryptamine (5-HT) can produce both vasoconstrictor and vasorelaxant effects in human coronary arteries and the response to 5-HT can be influenced by the presence of disease. The aim of the present study was to elucidate the 5-HT receptor subtypes responsible for mediating 5-HT-evoked contraction of human coronary arteries using pharmacological, molecular and immunocytochemical approaches. Normal human coronary arteries, with intact endothelium, were mounted in tissue baths, and the vascular responses to 5-HT and 5-HT receptor agonists were studied. The effects of 5-HT1 and 5-HT2 receptor antagonists on these responses were also studied. Expression of messenger ribonucleic acid (mRNA) encoding different 5-HT receptors in human coronary arteries, atrium, ventricle wall and epicardium was determined using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. The expression of 5-HT1B or 5-HT1D receptor protein was studied using subtype selective antibodies and standard immunocytochemical techniques. The rank order of 5-HT receptor agonist potency in causing vasoconstriction was 5-carboxamido tryptamine, (5-CT) > zolmitriptan = BW183C91 (N10-desmethyl zolmitriptan) = alpha-methyl-5-hydroxytryptamine (alpha-CH3-5-HT) = 5-HT = sumatriptan > 2-methyl-5-hydroxytryptamine (2-CH3-5-HT) = 8-hydroxy-DPAT (8-OH-DPAT). Alpha-CH3-5-HT, 5-CT, 5-HT, zolmitriptan and BW 183C91 were significantly more potent (approximately 3-fold) than sumatriptan and 2-CH3-5-HT, which in turn were more potent than 8-OH-DPAT. Ketanserin and methiothepin (5-HT2 and 5-HT1 receptor antagonists, respectively) caused parallel rightward shifts of the concentration-effect curves to alpha-CH3-5-HT or 5-CT, respectively, without changing the maximum contractile response. In human coronary arteries, atrium. ventricle and epicardium. RT-PCR products corresponding to the human 5-HT2A, 5-HT1B and 5-HT1F receptors were expressed in high levels, mRNAs coding for 5-HT7, 5-HT1A and 5-HT1D receptors were only weakly expressed. No 5-HT1F receptor mRNA was detected. In coronary arteries there was a differential expression of 5-HT1B versus 5-HT1D receptor mRNAs, with 5-HT1B mRNAs being found in greater abundance. Dense 5-HT1B-immunoreactivity was detected on smooth muscle layer within coronary artery, however, 5-HT1D-immunoreactivity was not detected. It is concluded that 5-HT-evoked contraction of human coronary arteries is most probably mediated via the activation of both 5-HT1B and 5-HT2A receptors.
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PMID:Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques. 1037 14

Using intracellular recordings, we have studied the action of 5-hydroxytryptamine (5-HT) on slices of human temporal, occipital and frontal cortex maintained in vitro. The recordings were usually made 1.2 to 1.5 mm down from the pial surface, in or around layer III. The action of 5-HT (30-50 microM) was studied on 21 cells (from 12 individuals) which had electrophysiological characteristics of glutamatergic pyramidal neurones. 5-HT depolarised the majority (11) of these cells with a median response of 5 mV. It produced a hyperpolarising response in five neurones (median=-4 mV) and a combined hyperpolarising/depolarising response in two others. No response was detected in three cells. The depolarising response was probably mediated by reducing a resting potassium conductance. Ketanserin (0.1 and 1.0 microM) and spiperone (1 microM) reduced the response indicating that it was likely mediated by 5-HT2A receptors. The hyperpolarising response was associated with the opening of ion channels and was blocked by the selective 5-HT1A receptor antagonist WAY-100635 (100 nM). 5-HT inhibited spontaneous synaptic potentials. This effect was reduced by ketanserin (1 microM) but not by WAY-100635 (100 nM). It is concluded that human neocortical neurones in vitro can be depolarised via 5-HT2A receptors and hyperpolarised via 5-HT1A receptors.
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PMID:Actions of 5-HT on human neocortical neurones in vitro. 1037 81

The effect of 5-hydroxytryptamine (5-HT) on phospholipase C (PLC)-mediated phosphoinositide (PI) hydrolysis and intracellular Ca2+ ([Ca2+]i) changes was investigated in canine cultured aorta smooth muscle cells (ASMCs). 5-HT-stimulated inositol phosphate (IP) accumulation was time and concentration dependent with a half-maximal response (pEC50) and a maximal response at 6.4 and 10 microM, n = 6, respectively. Stimulation of ASMCs by 5-HT produced an initial transient peak followed by a sustained, concentration-dependent elevation in [Ca+]i. The half-maximal response (pEC50) values of 5-HT for the peak and sustained plateau were 7.1 and 6.9, respectively. Ketanserin and mianserin (1 and 3 nM), 5-HT2A antagonists, were equipotent and had high affinity in antagonising the 5-HT-induced IP accumulation and [Ca2+]i change with pK(B) values of 8.6-9.1 and 8.6-9.4, respectively. In contrast, the concentration-effect curves of 5-HT-induced IP and [Ca2+]i responses were not shifted until the concentrations of NAN-190 and metoctopramide (5-HT1A and 5-HT3 receptor antagonists, respectively) were increased to as high as 1 microM with pK(B) values of 5.7-6.3 and 6.1-6.6, respectively, indicating that the 5-HT receptor-mediated responses had low affinity for these antagonists. Pre-treatment of ASMCs with pertussis toxin (100 ng/mL, 24 h) caused a significant inhibition of 5-HT-induced IP accumulation and [Ca2+]i change in ASMCs. Depletion of external Ca2+ or removal of Ca2+ by addition of EGTA led to a significant attenuation of IP accumulation and [Ca2+]i change induced by 5-HT. Influx of external Ca2+ was required for the 5-HT-induced responses, because Ca2+-channel blockers--verapamil, nifedipine and Ni2+--partly inhibited the 5-HT-induced IP accumulation and Ca2+ mobilisation. The sustained elevation of [Ca2+]i response to 5-HT was dependent on the presence of external Ca2+. Removal of external Ca2+ by addition of 5 mM EGTA during the sustained phase caused a rapid decline in [Ca2+]i to lower than the resting level. The sustained elevation of [Ca2+]i could then be evoked by addition of 1.8 mM Ca2+ in the continued presence of 5-HT. These results demonstrate that 5-HT directly stimulates PLC-mediated PI hydrolysis and Ca2+ mobilisation, at least in part, through a pertussis toxin-sensitive G protein in canine ASMCs. 5-HT2A receptors may be predominantly mediating IP accumulation, and subsequently IP-induced Ca2+ mobilisation may function as the transducing mechanism for 5-HT-stimulated contraction of aorta smooth muscle.
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PMID:5-Hydroxytryptamine-induced phosphoinositide hydrolysis and Ca2+ mobilisation in canine cultured aorta smooth muscle cells. 1037 10

We examined the effects of (R)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) on the monosynaptic spinal reflex in rats. In intact rats, (R)-8-OH-DPAT (10 microg/kg, i.v.) enhanced the amplitude of the monosynaptic reflex, whereas at 100 microg/kg, it reduced the amplitude. (S)-8-OH-DPAT enhanced the monosynaptic reflex dose-dependently. In spinalized rats, (R)-8-OH-DPAT produced dose-dependent inhibition, but the (S)-enantiomer did not affect the monosynaptic reflex. Pretreatment with spiroxatrine or 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190) inhibited (R)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did 5-hydroxytryptamine (5-HT) depletion. Ketanserin reduced the effect of (R)-8-OH-DPAT. These pretreatment regimens had no effect on the monosynaptic reflex depression produced by the (R)-enantiomer in intact and spinalized rats. Pretreatment with prazosin inhibited (S)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did noradrenaline and 5-HT depletion. These results suggest that supraspinal 5-HT1A receptors and the descending serotonergic system are involved in the stimulatory effect of (R)-8-OH-DPAT on the monosynaptic reflex, while both the descending serotonergic and noradrenergic systems, the latter acting via alpha1-adrenoceptors, are involved in the effect of the (S)-enantiomer on this reflex.
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PMID:Differential effects of (R)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin on the monosynaptic spinal reflex in rats. 1041 36

The effect of the selective dopamine D2 receptor agonist quinpirole, the selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT2A receptor antagonist ketanserin on catalepsy induced by atypical antipsychotics clozapine, risperidone, olanzapine and sertindole at higher doses was studied in rats. Haloperidol (0.5, 1 and 2 mg/kg), clozapine (50 and 75 mg/kg) and olanzapine (15 and 30 mg/kg) produced catalepsy dose-dependently while sertindole at doses up to 40 mg/kg failed to produce catalepsy in rats. However, sertindole (15, 30 and 45 mg/kg) produced a cataleptic effect in mice in a dose-dependent manner. At a high dose (5 mg/kg), risperidone produced catalepsy in rats. Quinpirole (0.05 and 0.1 mg/kg) reversed the cataleptic effect of haloperidol (2 mg/kg), risperidone (5 mg/kg), olanzapine (30 mg/kg) and sertindole (45 mg/kg). Quinpirole (0.05 and 0.1 mg/kg) reversed clozapine (75 mg/kg)-induced catalepsy. 8-OH-DPAT (0.15 and 0.3 mg/kg) dose-dependently reversed catalepsy induced by haloperidol (2 mg/kg) and risperidone (5 mg/kg) without affecting the cataleptic effect of olanzapine. However, the higher dose (0.45 mg/kg) of 8-OH-DPAT reversed it significantly. 8-OH-DPAT (0.3 mg/kg) reversed clozapine (75 mg/kg)-induced catalepsy. 8-OH-DPAT (0.15, 0.3 and 0.45 mg/kg) failed to reverse sertindole-induced catalepsy. Ketanserin (0.75 and 1.5 mg/kg) completely reversed catalepsy induced by haloperidol (2 mg/kg) and risperidone (5 mg/kg). Ketanserin (0.75 and 1.5 mg/kg) dose-dependently reversed olanzapine (30 mg/kg) and sertindole (45 mg/kg)-induced catalepsy without any effect on clozapine (75 mg/kg)-induced catalepsy. A higher dose (3 mg/kg) of ketanserin reversed clozapine-induced catalepsy. The present study suggests that atypical antipsychotics show fewer extrapyramidal symptoms (EPS) due to greater modulation of the serotonergic system. Therefore, an antipsychotic with dopamine D2/5-HT2A antagonistic action and 5-HT1A agonistic action may prove to be superior to the existing antipsychotics.
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PMID:Quinpirole, 8-OH-DPAT and ketanserin modulate catalepsy induced by high doses of atypical antipsychotics. 1066 5

Previous studies have shown that serotonin plays an inhibitory role in escape behavior induced by the aversive stimulation of the dorsal periaqueductal gray matter (DPAG). This defensive behavior has been related to panic disorder. Serotonin injected into the DPAG also inhibits escape behavior generated by the elevated T-maze. Besides escape, this test also measures inhibitory avoidance, a behavior associated with generalized anxiety disorder. We presently evaluate the role of the 5-HT1A, 5-HT2A and 5-HT2C receptors of the DPAG in the modulation of inhibitory avoidance and escape responses of rats submitted to the elevated T-maze. The results showed that intra-DPAG administration of the 5-HT1A receptor antagonist WAY-100635 and of the preferential antagonists of 5-HT2A and 5-HT2C receptors, ketanserin and SDZ SER 082, respectively, did not change rat behavior in the elevated T-maze. Intra-DPAG injection of serotonin inhibited escape, an effect blocked by local injection of these three antagonists. Ketanserin and SDZ SER 082, but not WAY-100635 antagonized the effect of serotonin in facilitating inhibitory avoidance. Intra-DPAG injection of the 5-HT1A agonist 8-OH-DPAT and of DOI, a preferential 5-HT2A agonist, also inhibited escape, an effect antagonized by WAY-100635 and ketanserin, respectively. The results indicate that serotonin in the DPAG exerts a phasic regulatory control on inhibitory avoidance and escape behaviors in the elevated T-maze. 5-HT1A and 5-HT2C receptors in the DPAG play an opposite role in inhibitory avoidance: whereas activation of the former receptors inhibits the acquisition of this response, activation of the latter facilitates it. Both 5-HT1A, 5-HT2A and 5-HT2C receptors seem to mediate the inhibitory action of serotonin on escape.
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PMID:Involvement of 5-HT1A and 5-HT2 receptors of the dorsal periaqueductal gray in the regulation of the defensive behaviors generated by the elevated T-maze. 1534 6


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