Primary Structure of the Human Platelet Serotonin 5‐HT<sub>2A</sub> Receptor: Identity with Frontal Cortex Serotonin 5‐HT<sub>2A</sub> Receptor

Cook, Edwin H.; Fletcher, Kathlyn E.; Wainwright, Mark S.; Marks, Nancy; Yan, Suxia; Leventhal, Bennett L.

doi:10.1046/j.1471-4159.1994.63020465.x

Cited by 138 publications

(38 citation statements)

References 17 publications

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“…As far as pedophilia is related to ICD and violence/aggression (see Introduction), our findings are in agreement with previous reports on increased number of platelet 5-HT2A receptors in aggression . The platelet 5-HT2A receptor is essentially identical to the corresponding structure in central 5-HT synapses (Cook et al 1994). However, other studies reported no significant association between platelet 5-HT2A receptor sites and measures of aggression (McBride et al 1994), whereas Blumensohn et al (1995) reported a reduction in the number of platelet 5-HT2A binding sites in delinquent adolescents.…”

Section: Discussionmentioning

confidence: 86%

Lower Baseline Plasma Cortisol and Prolactin together with Increased Body Temperature and Higher mCPP-Induced Cortisol Responses in Men with Pedophilia

Maes

2001

Neuropsychopharmacology

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There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to metachlorophenylpiperazine (mCPP) The sexual abuse of children (pedophilia) represents a significant proportion of about 25% of all sexual offences (Moller and Bier-Weiss 1995). Between 100,000 and 500,000 children in the United States are thought to be sexually molested annually (Fuller 1989). Pedophilia is one of the sexual deviation disorders or paraphilias, which are diagnosable psychiatric syndromes characterized by recurrent fantasies about deviant sex, intense associated cravings, and stereotypic behavioral responses (Berlin and Meinecke 1981). The DSM-IV (APA 1994) describes the paraphilias as an impulse control disorder (ICD) (Cosyns 1999). Indeed, patients with paraphilias experience tension or arousal before committing the sexual act, experience pleasure during the act and feel a release of tension after the act (Cosyns (Greenberg et al. 1996).Although there is a substantial evidence in the historical and anthropological record of pedophilia, there has been little research on the biological pathophysiology of pedophilia. Alterations in the metabolism of serotonin (5-HT) may play a role in the pathophysiology of paraphilias (Kafka 1997). 1) 5-HT is involved in male sexual behavior; 2) serotonergic agents, such as selective 5-HT reuptake inhibitors (SSRIs), can ameliorate paraphilic sexual behaviour (review: Balon 1998; Greenberg et al. 1996;Zonana and Norko 1999); and 3) there is an extensive number of clinical and animal studies supporting the hypothesis that a dysfunction of the 5-HT neurotransmitter system is an important factor in the underlying pathology of impulse control disorders (ICD) and aggression/violence (Linnoila et al. 1983;Markowitz and Coccaro 1995;Kavoussi et al. 1997;McElroy et al. 1995;Coccaro 1999).A number of studies report lower CSF 5-hydroxyindole-acetic acid (5-HIAA) in ICD and aggressive patients, such as impulsive offenders and fire setters (review: Virkkunen et al. 1989;Coccaro 1999). The prolactin responses induced by D-L-fenfluramine (an indirect 5-HT agonist which releases 5-HT) are significantly and inversely related with measurements of aggression (Coccaro et al. 1989;O'Keane et al. 1992). Several authors found inverse relationships between platelet 5-HT transporter binding and impulsivity/aggression (Simeon et al. 1992;Coccaro et al. 1996). Patients with episodic aggression show a significantly lower platelet [ 3 H]-5-HT uptake than controls (Brown et al. 1989). Coccaro et al. (1997) described a positive correlation between the number of platelet 5-HT2A receptor sites and measures of aggression, in personality-disordered patients. Tryptophan depletion in subjects with preexisting aggressive traits induces increased aggression (Cleare and Bond 1995). The ...

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Section: Discussionmentioning

confidence: 86%

Lower Baseline Plasma Cortisol and Prolactin together with Increased Body Temperature and Higher mCPP-Induced Cortisol Responses in Men with Pedophilia

Maes

2001

Neuropsychopharmacology

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“…32 In addition, primers were not designed within known polymorphic coding regions such as for the 5ht2a and 5ht6 receptors. 64,65 Given the existence of multiple isoforms of the a1a receptor, 66 primers that were specific for this subtype but did not pertain to a particular isoform were used. Amplification of cDNA for each receptor was undertaken using cDNA of human brain cortex, caudate nucleus or white blood cells as a positive control.…”

Section: Rna Extraction and First Strand Cdna Synthesismentioning

confidence: 99%

Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow

et al. 2003

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The antipsychotic drug clozapine, acts via interaction with selective neurotransmitter receptor systems. Its use however, is associated with lifethreatening agranulocytosis. The mechanism by which this occurs and its possible relationship with the drug's atypicality remain unclear. As a first step in identifying mechanistic pathways involved, profiling of neurotransmitter receptors on human neutrophils, mononuclear and bone marrow stromal cells as putative targets for clozapine-mediated toxicity was undertaken. Expression of mRNA encoding dopaminergic d2, d3, d4; serotonergic 5ht2a, 5ht2c, 5ht3, 5ht6, 5ht7; adrenergic a1a, a2; histaminergic h1 and muscarinic m1, m2, m3, m4, m5 receptors was analyzed by reverse transcription-polymerase chain reaction methods. While 5ht2c, 5ht6, m1 and m2 mRNA were undetected, the presence of the other receptors indicates sites at which clozapine could bind and induce toxicity of neutrophils and stromal components which regulate granulopoiesis. The functional significance of differential receptor expression while unknown, may argue for neural regulation of hematopoiesis.

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“…LSD binds to 5-HT receptors including 5-HT 2A and 5-HT 7 , both of which are expressed in the platelet (Cook et al, 1994) (Cook EH, unpublished observation). Murphy et al (2006) recently described decreased cortical 5-HT 2A binding in Asperger's syndrome, supporting the possible relevance of the platelet model.…”

Section: Introductionmentioning

confidence: 99%

Molecular Genetics of the Platelet Serotonin System in First-Degree Relatives of Patients with Autism

Cross

Kim

Weiss

et al. 2007

Neuropsychopharmacol

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Elevated platelet serotonin (5-hydroxytryptamine, 5-HT) is found in a subset of children with autism and in some of their first-degree relatives. Indices of the platelet serotonin system, including whole blood 5-HT, 5-HT binding affinity for the serotonin transporter (K m ), 5-HT uptake (V max ), and lysergic acid diethylamide (LSD) receptor binding, were previously studied in 24 first-degree relatives of probands with autism, half of whom were selected for elevated whole blood 5-HT levels. All subjects were then genotyped for selected polymorphisms at the SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 loci. Previous studies allowed an a priori prediction of SLC6A4 haplotypes that separated the subjects into three groups that showed significantly different 5-HT binding affinity (K m , p ¼ 0.005) and 5-HT uptake rate (V max , p ¼ 0.046). Genotypes at four individual polymorphisms in SLC6A4 were not associated with platelet 5-HT indices. Haplotypes at SLC6A4 and individual genotypes of polymorphisms at SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 showed no significant association with whole blood 5-HT. Haplotype analysis of two polymorphisms in TPH1 revealed a nominally significant association with whole blood 5-HT (p ¼ 0.046). These initial studies of indices of the 5-HT system with several single-nucleotide polymorphisms at loci in this system generate hypotheses for testing in other samples.

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Primary Structure of the Human Platelet Serotonin 5‐HT_2A Receptor: Identity with Frontal Cortex Serotonin 5‐HT_2A Receptor

Cited by 138 publications

References 17 publications

Lower Baseline Plasma Cortisol and Prolactin together with Increased Body Temperature and Higher mCPP-Induced Cortisol Responses in Men with Pedophilia

Lower Baseline Plasma Cortisol and Prolactin together with Increased Body Temperature and Higher mCPP-Induced Cortisol Responses in Men with Pedophilia

Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow

Molecular Genetics of the Platelet Serotonin System in First-Degree Relatives of Patients with Autism

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Primary Structure of the Human Platelet Serotonin 5‐HT2A Receptor: Identity with Frontal Cortex Serotonin 5‐HT2A Receptor

Cited by 138 publications

References 17 publications

Lower Baseline Plasma Cortisol and Prolactin together with Increased Body Temperature and Higher mCPP-Induced Cortisol Responses in Men with Pedophilia

Lower Baseline Plasma Cortisol and Prolactin together with Increased Body Temperature and Higher mCPP-Induced Cortisol Responses in Men with Pedophilia

Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow

Molecular Genetics of the Platelet Serotonin System in First-Degree Relatives of Patients with Autism

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Primary Structure of the Human Platelet Serotonin 5‐HT_2A Receptor: Identity with Frontal Cortex Serotonin 5‐HT_2A Receptor