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

Experimental lesions followed by binding of [3H]4-trans-2-carboxy-5,7-dichloro-4-phenylamino-carbonylamino-1,2 ,3,4- tetrahydroquinoline ([3H]L-689,560, a novel ligand that binds to the glycine modulatory site), [3H]glycine and [3H]glutamate (N-methyl-D-aspartate (NMDA) sensitive) to cryostat sections and quantitative autoradiography were used to investigate the cellular localization of the NMDA receptor complex in the neocortex of the rat. The lesions were produced by intrastriatal injections of either volkensin (2 and 6 ng) or ricin (10 ng): both are suicide transport agents but only the former is retrogradely transported in the CNS. The binding of [3H]L-689,560 was significantly reduced in rats receiving 2 or 6 ng volkensin in deep cortical layers of Fr1/Fr2 ipsilateral to the striatal lesion. Similar reductions were also seen in [3H]glycine and [3H]glutamate binding, but only in rats receiving 6 ng volkensin. Quantitative histological analysis had previously revealed a loss of large infragranular pyramidal neurones with sparing of both interneurones and supragranular pyramidal neurones. There were no significant reductions in binding of any ligand in the superficial layers. In cortical areas Par1/Par2, [3H]L-689,560 was also significantly reduced in deep layers but only in rats receiving 6 ng volkensin. Binding was also reduced in the superficial layers by contrast to Fr1/Fr2. [3H]Glycine and [3H]glutamate binding were unaffected in this area. Binding of [3H]L-689,560 was unaffected in any area following intrastriatal ricin injection. The present study indicates that the NMDA receptor complex is present on pyramidal cells forming the corticofugal pathways. This is discussed in terms of the 5-HT1A receptor which is enriched on these cells.
 ...
PMID:NMDA receptors assessed by autoradiography with [3H]L-689,560 are present but not enriched on corticofugal-projecting pyramidal neurones. 136 17

The density of 5-HT1A binding using 3H-8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) as binding ligand, was studied in human frontal cortex of suicide victims and normal controls who died due to medical disease or accidentally. There was no difference in the maximum number of binding site (Bmax) or Kd (an inverse measure of affinity) of 5-HT1A receptor binding sites between normal controls and the entire group of suicide victims. However, nonviolent suicides had significantly higher Bmax (22-25%) compared to both controls and violent suicides. A negative correlation between age and Bmax of 5-HT1A binding sites was found in male controls but not in female controls or suicide victims. This relationship was less apparent among the male controls over age 60.
 ...
PMID:Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims. 183 90

Although suicide was traditionally considered an extreme response to stress, with the most frequent stress being depressive illness, severity of depression does not distinguish those who commit suicide from non-suicide attempters. A biological role involving the serotonergic system, possibly associated with a genetic risk factor, has been postulated. Low levels of 5-HT and 5-HIAA have been found in post-mortem examinations of brain-stem tissues of suicide victims (levels in cortical tissue were generally normal). An increased number of 5-HT2 receptors was found in the pre-frontal cortex of suicide victims, such upregulation having been demonstrated in induced 5-HT deficiency states; 5-HT1A receptors were also increased. Receptor populations may be altered by chronic psychotropic medication; e.g. 5-HT2 downregulation occurs following administration of antidepressants. There is some indication that the adrenergic system may be involved as well, but this will require further study. Antidepressant drugs may be effective in preventing suicide in patients with non-depressive syndromes who exhibit suicidal behaviour.
 ...
PMID:Evidence for the 5-HT hypothesis of suicide. A review of post-mortem studies. 269 42

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors.
 ...
PMID:Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates. 778 83

We report on 5-HT1A, 5-HT1D, and 5-HT2 binding sites in 23 control subjects and 18 suicide victims subdivided according to the method of death and the previous existence of depressive symptoms. No difference in maximum binding (Bmax) or binding affinity (Kd) was found between the control and overall suicide groups for the binding sites studied. The drug overdose subgroup showed, however, a significant decrease in the 5-HT1A binding affinity, probably explained by the higher sensitivity of this binding site to the acute administration of tricyclic antidepressants. A significant decrease in 5-HT1D binding affinity was also found in the depressed suicides, together with a significant decrease in the number of 5-HT1D binding sites in the nondepressed suicides. Further studies should be carried out on the 5-HT1D binding site as it might represent a new tool in the understanding of the depressive illness.
 ...
PMID:Brain 5-HT1A, 5-HT1D, and 5-HT2 receptors in suicide victims. 801 97

Pyramidal neurones of the neocortex have been implicated in a number of neuropsychiatric diseases, such as Alzheimer's disease. Markers that may identify these cells have been investigated using a novel technique. A subpopulation of corticifugal neocortical pyramidal neurones was destroyed by the unilateral striatal injection of volkensin, a toxin that undergoes retrograde suicide transport from the site of injection. Striatal volkensin injections produced significant reductions in the number of large pyramidal neurones of the infragranular cortical layer. The selectivity of the lesion was demonstrated by the preservation of cells containing glutamic acid decarboxylase mRNA, which are considered to be cortical interneurones. Ricin, another toxic lectin, but effective as a suicide transport agent exclusively in the PNS, produced local striatal damage but no cortical cell loss. In autoradiographic binding studies of animals treated with volkensin, binding in deep neocortical layers of [3H]8-hydroxy-2-(n-dipropylamino) tetralin ([3H]8-OH-DPAT) to 5-HT1A but not of [3H]ketanserin to 5-HT2 receptors was significantly reduced. The N-methyl-D-aspartate receptor complex was investigated using the novel glycine site antagonist [3H]L-689,560, and the muscarinic M1 receptor using [3H]pirenzepine. Significant reductions in binding of [3H]L-689,560 and [3H]pirenzepine were observed in the deep neocortical layers of the animals that had been injected with volkensin. The rank order of the ligands as effective markers for this subpopulation of pyramidal neurones was [3H]8-OH-DPAT >> [3H]pirenzepine > [3H]L-689,560 >> [3H]ketanserin. These findings are thought to have advanced the understanding of the biology of pyramidal neurones. Implications for in vivo imaging treatment of neuropsychiatric conditions such as Alzheimer's disease are discussed.
 ...
PMID:Neurotransmitter receptors of rat cortical pyramidal neurones: implications for in vivo imaging and therapy. 839 Oct 81

Altered serotonin indices have been reported in the brain of suicide victims. We sought to localize the changes in presynaptic and postsynaptic serotonin receptors and identify an area of prefrontal cortex that may influence suicide risk. Quantitative autoradiography was performed in coronal sections of prefrontal cortex to determine whether serotonin 5-HT1A receptor (postsynaptic in cortex) and serotonin transporter (presynaptic) binding are different in suicide victims compared to matched controls. 5-HT1A receptor binding was higher in 85 of the 103 sampled areas in the suicide group (n = 18 pairs; P < 0.0001). The increase ranged from 17 to 30%. The increase was more pronounced in the ventrolateral prefrontal cortex. Serotonin transporter binding was found to be lower in the suicide group in all but one of the 43 sampled regions (n = 22 pairs; P < 0.0001). The reduction in binding was most pronounced in the ventrolateral prefrontal cortex, where the difference between suicides and controls ranged between 15 and 27%. Serotonin transporter and 5-HT1A binding were negatively correlated (r = -0.35 to -0.44, P = 0.04 to 0.007) within the same brain areas, suggesting common regulatory factors with opposite effects on binding to the two receptors. We conclude that suicide victims have an abnormality in the serotonin system involving predominantly the ventrolateral prefrontal cortex, and hypothesize that the serotonergic dysfunction in this brain region contributes to the risk for suicidal behavior.
 ...
PMID:Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. 854 98

The prevailing neurochemical theory about biological correlates of suicidal behavior focuses on the serotonergic system. In this study, we assessed the cortisol, ACTH, GH, prolactin and temperature responses to flesinoxan, a5-HT1A agonist, in 30 DSM-III-R major depressed inpatients subgrouped into suicide attempters (n = 15) and nonattempters (n = 15). The patients were assessed after a drug-free period of at least 3 weeks. A subsample of 16 patients completed the Buss-Durkee Hostility Inventory as a measure of impulsive aggressive behavior. Mean delta cortisol responses to flesinoxan were significantly lower in the group of depressed patients with a history of suicide attempts than in the group without history of suicidal behavior: for the delta cortisol values 14.5 +/- 16.3 micrograms/l vs 101 +/- 94 micrograms/l (F = 8.9, df = 5.25, p = 0.006). There was also a very significant difference between suicide attempters and nonattempters for the temperature (delta T degrees) responses to flesinoxan: 0.20 +/- 0.24 degrees C vs. 0.60 +/- 0.24 degrees C (F = 18.1, df = 5.25, p = 0.0003). Hormonal and temperature responses to flesinoxan were not correlated with BDHI irritability or assault subscale scores. The results of the present study support the implication of the serotonergic system, particularly 5-HT1A receptors, in the control of self-directed aggressive behavior. Moreover, in depressed patients, serotonergic abnormalities do not appear to be related to aggressive behavior.
 ...
PMID:The flesinoxan 5-HT1A receptor challenge in major depression and suicidal behavior. 861 6

Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been implicated in the pathophysiology of suicide. Brain samples were collected at autopsy from suicide victims with a current episode of major depression and matched comparison subjects who died of natural or accidental causes. Retrospective psychiatric assessments were collected from knowledgeable informants for all suicide victims and most of the comparison subjects. Psychiatric diagnoses were determined according to DSM-III-R criteria. Any subjects with current psychoactive substance use disorders were excluded. Quantitative receptor autoradiography was used in serial sections of the right prefrontal cortex (area 10) and hippocampus to measure the binding of [3H]8-hydroxy-2-(di-n-propyl)-aminotetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and [3H]ketanserin to 5-HT2A receptors. Analysis of covariance was used to compare control subjects and suicide victims with major depression. The age of subjects, the time from death to freezing the tissue (postmortem interval), and the storage time of tissues in the freezer were used as covariates in the analyses. There were no significant differences between suicide victims with major depression and comparison subjects in 5-HT1A or 5-HT2A receptors in area 10 of the right prefrontal cortex or the hippocampus. The current results suggest that the number of 5-HT1A and 5-HT2A receptors in the right prefrontal cortex (area 10) or hippocampus are not different in suicide victims with major depression.
 ...
PMID:Serotonin receptors in suicide victims with major depression. 901 99

5-HT1A receptor binding sites were measured, by saturation binding with [3H]8-OH-DPAT, in frontal and occipital cortex, hippocampus and amygdala obtained at post-mortem examination from suicide victims with a firm retrospective diagnosis of depression, and matched controls. The number of 5-HT1A binding sites did not differ significantly between suicides and controls, either in the total sample or when the suicides were divided on the basis of violence of death or recent antidepressant treatment.
 ...
PMID:5-HT1A receptor binding sites in post-mortem brain samples from depressed suicides and controls. 910 61


1 2 3 4 5 Next >>