The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
Claudia Martini - One of the best experts on this subject based on the ideXlab platform.
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Receptor crosstalk haloperidol treatment enhances a 2a adenosine Receptor Functioning in a transfected cell model
Purinergic Signalling, 2010Co-Authors: Maria Letizia Trincavelli, Serena Cuboni, Mario Catena Dellosso, Roberto Maggio, Karlnorbert Klotz, Francesca Novi, Anna Panighini, Simona Daniele, Claudia MartiniAbstract:A2A adenosine Receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A2A adenosine Receptors are regulated by D2 dopamine Receptor ligands. These two Receptors are co-expressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A2A adenosine Receptor functional responses caused by the chronic blockade/activation of D2 dopamine Receptors should be considered to optimise the therapeutic effectiveness of dopaminergic agents and to reduce any possible side effects. In the present paper, we investigated the regulation of A2A adenosine Receptors induced by antipsychotic drugs, commonly acting as D2 dopamine Receptor antagonists, in a cellular model co-expressing both A2A and D2 Receptors. Our data suggest that the treatment of cells with the classical antipsychotic haloperidol increased both the affinity and responsiveness of the A2A Receptor and also affected the degree of A2A–D2 Receptor heterodimerisation. In contrast, an atypical antipsychotic, clozapine, had no effect on A2A adenosine Receptor parameters, suggesting that the two classes of drugs have different effects on adenosine–dopamine Receptor interaction. Modifications to A2A adenosine Receptors may play a significant role in determining cerebral adenosine effects during the chronic administration of antipsychotics in psychiatric diseases and may account for the efficacy of A2A adenosine Receptor ligands in pathologies associated with dopaminergic system dysfunction. Electronic supplementary material The online version of this article (doi:10.1007/s11302-010-9201-z) contains supplementary material, which is available to authorized users.
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regulation of a1 adenosine Receptor Functioning induced by p2y1 purinergic Receptor activation in human astroglial cells
Journal of Neuroscience Research, 2008Co-Authors: Ilaria Tonazzini, Maria Letizia Trincavelli, Marina Montali, Claudia MartiniAbstract:In the rat brain, a heteromeric association between adenosine A 1 and purinergic P2Y 1 Receptors has been demonstrated. It is suggested that this association plays an important role in the control of purine-mediated responses during pathophysiological conditions. Recently, we have demonstrated that these Receptors colocalize on glutamatergic synaptic and astroglial membranes in rat hippocampus and reciprocally interact, thus modulating their functional responses at the G protein coupling level. In the present work, by means of immunoprecipitation studies, we demonstrated that A 1 and P2Y 1 Receptors are present in human astroglial cells (ADF) and aggregate to form a multimeric complex. P2Y 1 Receptor activation by its agonist, 2-methyl-thio-adenosine 5'-diphosphate (MeSADP), induced a time-dependent reduction in agonist-mediated A 1 Receptor functional responses, causing a drop in A 1 Receptor agonist potency to promote Receptor-G protein coupling and to inhibit the adenylate cyclase pathway. These effects appeared to be selectively mediated by P2Y 1 Receptor activation and probably occurred as a consequence of a direct Receptor-Receptor interaction at the plasma membrane level. These results indicated that P2Y 1 Receptor activation induces A 1 Receptor heterologous desensitization. The interaction between A 1 and P2Y 1 Receptors may play an important role in the purinergic signaling cascade in astrocytes, which are involved in cell-to-cell communication and in control of synaptic transmission, particularly during pathological conditions, when large amounts of purines are released.
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regulation of a 2a adenosine Receptor expression and Functioning following permanent focal ischemia in rat brain
Journal of Neurochemistry, 2007Co-Authors: Maria Letizia Trincavelli, Serena Cuboni, Alessia Melani, Sara Guidi, Sara Cipriani, Felicita Pedata, Claudia MartiniAbstract:Ischemia, through modulation of adenosine Receptors (ARs), may influence adenosine-mediated-cellular responses. In the present study, we investigated the modulation of rat A2A Receptor expression and Functioning, in rat cerebral cortex and striatum, following in vivo focal ischemia (24 h). In cortex, middle cerebral artery occlusion did not induce any alterations in A2A Receptor binding and Functioning. On the contrary, in striatum, a significant decrease in A2A ligand affinity, associated with an increase in Receptor density, were detected. In striatum, ischemia also induced a significant reduction both in G protein pool and in A2A Receptor-G protein coupling. On the contrary, A2A Receptor functional responsiveness, measured as stimulation of adenylyl cyclise, was not affected by ischemia, suggesting Receptor up-regulation may represent a compensatory mechanism to maintain Receptor Functioning during cerebral damage. Immunohistochemical study showed that following 24 h middle cerebral artery occlusion, A2A ARs were definitely expressed both on neurons and activated microglia in ischemic striatum and cortex, but were not detected on astrocytes. In the non-ischemic hemisphere and in sham-operated rats A2A ARs were barely detected. Modifications of ARs may play a significant role in determining adenosine effects during ischemia and therefore should be taken into account when evaluating time-dependent protective effects of specific A2A active compounds.
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regulation of a2b adenosine Receptor Functioning by tumour necrosis factor a in human astroglial cells
Journal of Neurochemistry, 2004Co-Authors: Maria Letizia Trincavelli, M Marroni, D Tuscano, Stefania Ceruti, Alessia Mazzola, Nico Mitro, Maria P Abbracchio, Claudia MartiniAbstract:Low-affinity A2B adenosine Receptors (A2B ARs), which are expressed in astrocytes, are mainly activated during brain hypoxia and ischaemia, when large amounts of adenosine are released. Cytokines, which are also produced at high levels under these conditions, may regulate Receptor responsiveness. In the present study, we detected A2B AR in human astrocytoma cells (ADF) by both immunoblotting and real-time PCR. Functional studies showed that the Receptor stimulated adenylyl cyclase through Gs proteins. Moreover, A2B ARs were phosphorylated and desensitized following stimulation of the Receptors with high agonist concentration. Tumour necrosis factor alpha (TNF-α) treatment (24- h) increased A2B AR functional response and Receptor G protein coupling, without any changes in Receptor protein and mRNA levels. TNF-α markedly reduced agonist-dependent Receptor phosphorylation on threonine residues and attenuated agonist-mediated A2B ARs desensitization. In the presence of TNF-α, A2B AR stimulation in vitro induced the elongation of astrocytic processes, a typical morphological hallmark of in vivo reactive astrogliosis. This event was completely prevented by the selective A2B AR antagonist MRS 1706 and required the presence of TNF-α. These results suggest that, in ADF cells, TNF-α selectively modulates A2B AR coupling to G proteins and Receptor functional response, providing new insights to clarify the pathophysiological role of A2B AR in response to brain damage.
Marcel D. Waldinger - One of the best experts on this subject based on the ideXlab platform.
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the 5 ht a Receptor c 1019 g polymorphism influences the intravaginal ejaculation latency time in dutch caucasian men with lifelong premature ejaculation
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Paddy K. C. Janssen, Ron H.n. Van Schaik, Aeilko H Zwinderman, Berend Olivier, Marcel D. WaldingerAbstract:It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5‑hydroxytryptamine (HT)2C Receptor Functioning. The aim of this study was to investigate the relationship of Cys23Ser 5‑HT2C Receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1‑month period. All men were genotyped for Cys23Ser 5‑HT2C Receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5‑HT2C Receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10–20, 20–30 and 30–60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5‑HT2C Receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3–27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3–80.4 s) (P = 0.03). It is concluded that Cys23Ser 5‑HT2C Receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
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serotonin transporter promoter region 5 httlpr polymorphism is associated with the intravaginal ejaculation latency time in dutch men with lifelong premature ejaculation
The Journal of Sexual Medicine, 2009Co-Authors: Paddy K. C. Janssen, Aeilko H Zwinderman, Berend Olivier, Steven C Bakker, Janos Rethelyi, Daan J Touw, Marcel D. WaldingerAbstract:ABSTRACT Introduction Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission and 5-HT Receptor Functioning. Aim To investigate the relationship between 5-HT transporter gene-linked polymorphism (5-HTTLPR) and short IELTs in men with lifelong PE. Methods A prospective study was conducted in 89 Dutch Caucasian men with lifelong PE. IELT during coitus was assessed by stopwatch over a 1-month period. Controls consisted of 92 Dutch Caucasian men. All men with LPE were genotyped for a 5-HTT-promoter polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of 5-HTTLPR polymorphism were compared between patients and controls. Association between LL, SL, and SS genotypes, and the natural logarithm of the IELT in men with LPE was investigated. Main Outcome Measures IELT measured by stopwatch, 5-HTTLPR polymorphism. Results In men with lifelong PE, the geometric mean, median, and natural mean IELTs were 21, 26, and 32 seconds, respectively. There were no significant differences in the 5-HTT polymorphism alleles and genotypes between 89 Dutch Caucasian men with LPE (S 47%, L 53%/LL 29%, SL 48%, SS 22%) and 92 Dutch Caucasian controls (S 48%, L 52%/LL 29%, SL 45%, SS 26%). In men with lifelong PE there was a statistically significant difference between LL, SL, and SS genotypes in their geometric mean IELT ( P ≤ 0.027); the LL genotypes had significantly shorter IELTs than the SS and SL genotypes. Conclusions The 5-HTTLPR polymorphism is associated with significant effects on the latency to ejaculate in men with lifelong PE. Men with SS and SL genotypes have 100% and 90% longer ejaculation time, respectively than men with LL genotypes. Janssen PKC, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, and Waldinger MD. Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation.
Berend Olivier - One of the best experts on this subject based on the ideXlab platform.
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the 5 ht a Receptor c 1019 g polymorphism influences the intravaginal ejaculation latency time in dutch caucasian men with lifelong premature ejaculation
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Paddy K. C. Janssen, Ron H.n. Van Schaik, Aeilko H Zwinderman, Berend Olivier, Marcel D. WaldingerAbstract:It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5‑hydroxytryptamine (HT)2C Receptor Functioning. The aim of this study was to investigate the relationship of Cys23Ser 5‑HT2C Receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1‑month period. All men were genotyped for Cys23Ser 5‑HT2C Receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5‑HT2C Receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10–20, 20–30 and 30–60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5‑HT2C Receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3–27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3–80.4 s) (P = 0.03). It is concluded that Cys23Ser 5‑HT2C Receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
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serotonin transporter promoter region 5 httlpr polymorphism is associated with the intravaginal ejaculation latency time in dutch men with lifelong premature ejaculation
The Journal of Sexual Medicine, 2009Co-Authors: Paddy K. C. Janssen, Aeilko H Zwinderman, Berend Olivier, Steven C Bakker, Janos Rethelyi, Daan J Touw, Marcel D. WaldingerAbstract:ABSTRACT Introduction Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission and 5-HT Receptor Functioning. Aim To investigate the relationship between 5-HT transporter gene-linked polymorphism (5-HTTLPR) and short IELTs in men with lifelong PE. Methods A prospective study was conducted in 89 Dutch Caucasian men with lifelong PE. IELT during coitus was assessed by stopwatch over a 1-month period. Controls consisted of 92 Dutch Caucasian men. All men with LPE were genotyped for a 5-HTT-promoter polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of 5-HTTLPR polymorphism were compared between patients and controls. Association between LL, SL, and SS genotypes, and the natural logarithm of the IELT in men with LPE was investigated. Main Outcome Measures IELT measured by stopwatch, 5-HTTLPR polymorphism. Results In men with lifelong PE, the geometric mean, median, and natural mean IELTs were 21, 26, and 32 seconds, respectively. There were no significant differences in the 5-HTT polymorphism alleles and genotypes between 89 Dutch Caucasian men with LPE (S 47%, L 53%/LL 29%, SL 48%, SS 22%) and 92 Dutch Caucasian controls (S 48%, L 52%/LL 29%, SL 45%, SS 26%). In men with lifelong PE there was a statistically significant difference between LL, SL, and SS genotypes in their geometric mean IELT ( P ≤ 0.027); the LL genotypes had significantly shorter IELTs than the SS and SL genotypes. Conclusions The 5-HTTLPR polymorphism is associated with significant effects on the latency to ejaculate in men with lifelong PE. Men with SS and SL genotypes have 100% and 90% longer ejaculation time, respectively than men with LL genotypes. Janssen PKC, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, and Waldinger MD. Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation.
Maria Letizia Trincavelli - One of the best experts on this subject based on the ideXlab platform.
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Receptor crosstalk haloperidol treatment enhances a 2a adenosine Receptor Functioning in a transfected cell model
Purinergic Signalling, 2010Co-Authors: Maria Letizia Trincavelli, Serena Cuboni, Mario Catena Dellosso, Roberto Maggio, Karlnorbert Klotz, Francesca Novi, Anna Panighini, Simona Daniele, Claudia MartiniAbstract:A2A adenosine Receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A2A adenosine Receptors are regulated by D2 dopamine Receptor ligands. These two Receptors are co-expressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A2A adenosine Receptor functional responses caused by the chronic blockade/activation of D2 dopamine Receptors should be considered to optimise the therapeutic effectiveness of dopaminergic agents and to reduce any possible side effects. In the present paper, we investigated the regulation of A2A adenosine Receptors induced by antipsychotic drugs, commonly acting as D2 dopamine Receptor antagonists, in a cellular model co-expressing both A2A and D2 Receptors. Our data suggest that the treatment of cells with the classical antipsychotic haloperidol increased both the affinity and responsiveness of the A2A Receptor and also affected the degree of A2A–D2 Receptor heterodimerisation. In contrast, an atypical antipsychotic, clozapine, had no effect on A2A adenosine Receptor parameters, suggesting that the two classes of drugs have different effects on adenosine–dopamine Receptor interaction. Modifications to A2A adenosine Receptors may play a significant role in determining cerebral adenosine effects during the chronic administration of antipsychotics in psychiatric diseases and may account for the efficacy of A2A adenosine Receptor ligands in pathologies associated with dopaminergic system dysfunction. Electronic supplementary material The online version of this article (doi:10.1007/s11302-010-9201-z) contains supplementary material, which is available to authorized users.
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regulation of a1 adenosine Receptor Functioning induced by p2y1 purinergic Receptor activation in human astroglial cells
Journal of Neuroscience Research, 2008Co-Authors: Ilaria Tonazzini, Maria Letizia Trincavelli, Marina Montali, Claudia MartiniAbstract:In the rat brain, a heteromeric association between adenosine A 1 and purinergic P2Y 1 Receptors has been demonstrated. It is suggested that this association plays an important role in the control of purine-mediated responses during pathophysiological conditions. Recently, we have demonstrated that these Receptors colocalize on glutamatergic synaptic and astroglial membranes in rat hippocampus and reciprocally interact, thus modulating their functional responses at the G protein coupling level. In the present work, by means of immunoprecipitation studies, we demonstrated that A 1 and P2Y 1 Receptors are present in human astroglial cells (ADF) and aggregate to form a multimeric complex. P2Y 1 Receptor activation by its agonist, 2-methyl-thio-adenosine 5'-diphosphate (MeSADP), induced a time-dependent reduction in agonist-mediated A 1 Receptor functional responses, causing a drop in A 1 Receptor agonist potency to promote Receptor-G protein coupling and to inhibit the adenylate cyclase pathway. These effects appeared to be selectively mediated by P2Y 1 Receptor activation and probably occurred as a consequence of a direct Receptor-Receptor interaction at the plasma membrane level. These results indicated that P2Y 1 Receptor activation induces A 1 Receptor heterologous desensitization. The interaction between A 1 and P2Y 1 Receptors may play an important role in the purinergic signaling cascade in astrocytes, which are involved in cell-to-cell communication and in control of synaptic transmission, particularly during pathological conditions, when large amounts of purines are released.
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regulation of a 2a adenosine Receptor expression and Functioning following permanent focal ischemia in rat brain
Journal of Neurochemistry, 2007Co-Authors: Maria Letizia Trincavelli, Serena Cuboni, Alessia Melani, Sara Guidi, Sara Cipriani, Felicita Pedata, Claudia MartiniAbstract:Ischemia, through modulation of adenosine Receptors (ARs), may influence adenosine-mediated-cellular responses. In the present study, we investigated the modulation of rat A2A Receptor expression and Functioning, in rat cerebral cortex and striatum, following in vivo focal ischemia (24 h). In cortex, middle cerebral artery occlusion did not induce any alterations in A2A Receptor binding and Functioning. On the contrary, in striatum, a significant decrease in A2A ligand affinity, associated with an increase in Receptor density, were detected. In striatum, ischemia also induced a significant reduction both in G protein pool and in A2A Receptor-G protein coupling. On the contrary, A2A Receptor functional responsiveness, measured as stimulation of adenylyl cyclise, was not affected by ischemia, suggesting Receptor up-regulation may represent a compensatory mechanism to maintain Receptor Functioning during cerebral damage. Immunohistochemical study showed that following 24 h middle cerebral artery occlusion, A2A ARs were definitely expressed both on neurons and activated microglia in ischemic striatum and cortex, but were not detected on astrocytes. In the non-ischemic hemisphere and in sham-operated rats A2A ARs were barely detected. Modifications of ARs may play a significant role in determining adenosine effects during ischemia and therefore should be taken into account when evaluating time-dependent protective effects of specific A2A active compounds.
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regulation of a2b adenosine Receptor Functioning by tumour necrosis factor a in human astroglial cells
Journal of Neurochemistry, 2004Co-Authors: Maria Letizia Trincavelli, M Marroni, D Tuscano, Stefania Ceruti, Alessia Mazzola, Nico Mitro, Maria P Abbracchio, Claudia MartiniAbstract:Low-affinity A2B adenosine Receptors (A2B ARs), which are expressed in astrocytes, are mainly activated during brain hypoxia and ischaemia, when large amounts of adenosine are released. Cytokines, which are also produced at high levels under these conditions, may regulate Receptor responsiveness. In the present study, we detected A2B AR in human astrocytoma cells (ADF) by both immunoblotting and real-time PCR. Functional studies showed that the Receptor stimulated adenylyl cyclase through Gs proteins. Moreover, A2B ARs were phosphorylated and desensitized following stimulation of the Receptors with high agonist concentration. Tumour necrosis factor alpha (TNF-α) treatment (24- h) increased A2B AR functional response and Receptor G protein coupling, without any changes in Receptor protein and mRNA levels. TNF-α markedly reduced agonist-dependent Receptor phosphorylation on threonine residues and attenuated agonist-mediated A2B ARs desensitization. In the presence of TNF-α, A2B AR stimulation in vitro induced the elongation of astrocytic processes, a typical morphological hallmark of in vivo reactive astrogliosis. This event was completely prevented by the selective A2B AR antagonist MRS 1706 and required the presence of TNF-α. These results suggest that, in ADF cells, TNF-α selectively modulates A2B AR coupling to G proteins and Receptor functional response, providing new insights to clarify the pathophysiological role of A2B AR in response to brain damage.
Paddy K. C. Janssen - One of the best experts on this subject based on the ideXlab platform.
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the 5 ht a Receptor c 1019 g polymorphism influences the intravaginal ejaculation latency time in dutch caucasian men with lifelong premature ejaculation
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Paddy K. C. Janssen, Ron H.n. Van Schaik, Aeilko H Zwinderman, Berend Olivier, Marcel D. WaldingerAbstract:It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5‑hydroxytryptamine (HT)2C Receptor Functioning. The aim of this study was to investigate the relationship of Cys23Ser 5‑HT2C Receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1‑month period. All men were genotyped for Cys23Ser 5‑HT2C Receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5‑HT2C Receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10–20, 20–30 and 30–60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5‑HT2C Receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3–27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3–80.4 s) (P = 0.03). It is concluded that Cys23Ser 5‑HT2C Receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
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serotonin transporter promoter region 5 httlpr polymorphism is associated with the intravaginal ejaculation latency time in dutch men with lifelong premature ejaculation
The Journal of Sexual Medicine, 2009Co-Authors: Paddy K. C. Janssen, Aeilko H Zwinderman, Berend Olivier, Steven C Bakker, Janos Rethelyi, Daan J Touw, Marcel D. WaldingerAbstract:ABSTRACT Introduction Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission and 5-HT Receptor Functioning. Aim To investigate the relationship between 5-HT transporter gene-linked polymorphism (5-HTTLPR) and short IELTs in men with lifelong PE. Methods A prospective study was conducted in 89 Dutch Caucasian men with lifelong PE. IELT during coitus was assessed by stopwatch over a 1-month period. Controls consisted of 92 Dutch Caucasian men. All men with LPE were genotyped for a 5-HTT-promoter polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of 5-HTTLPR polymorphism were compared between patients and controls. Association between LL, SL, and SS genotypes, and the natural logarithm of the IELT in men with LPE was investigated. Main Outcome Measures IELT measured by stopwatch, 5-HTTLPR polymorphism. Results In men with lifelong PE, the geometric mean, median, and natural mean IELTs were 21, 26, and 32 seconds, respectively. There were no significant differences in the 5-HTT polymorphism alleles and genotypes between 89 Dutch Caucasian men with LPE (S 47%, L 53%/LL 29%, SL 48%, SS 22%) and 92 Dutch Caucasian controls (S 48%, L 52%/LL 29%, SL 45%, SS 26%). In men with lifelong PE there was a statistically significant difference between LL, SL, and SS genotypes in their geometric mean IELT ( P ≤ 0.027); the LL genotypes had significantly shorter IELTs than the SS and SL genotypes. Conclusions The 5-HTTLPR polymorphism is associated with significant effects on the latency to ejaculate in men with lifelong PE. Men with SS and SL genotypes have 100% and 90% longer ejaculation time, respectively than men with LL genotypes. Janssen PKC, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, and Waldinger MD. Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation.
