Home About us Contact
|
Home About us Contact | ||
|
|
||
Reuptake Transporter (reuptake + transporter)
Kinds of Reuptake Transporter Selected AbstractsORIGINAL RESEARCH,BASIC SCIENCE: Effect of the Destruction of Cells Containing the Serotonin Reuptake Transporter on Urethrogenital ReflexesTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2007Karla Gravitt BSc ABSTRACT Introduction., The urethrogenital (UG) reflex is an autonomic and somatic response that mimics some of the physiological changes seen during ejaculation. The UG reflex is tonically inhibited by neurons in the ventral medulla, an area containing serotonin neurons. Aim., To examine the effect of lesions of brain neurons containing the serotonin reuptake transporter (SERT) on ejaculatory-like reflexes. Methods., Anti-SERT saporin (80 nL, 1 mM) or saline was injected bilaterally into the ventrolateral medulla of male Sprague,Dawley rats. Ten to 18 days later, animals were deeply anesthetized and the presence of the UG reflex was examined before and after acute spinal cord transection (T9,10). Following the experiment the presence and number of serotonin and norepinephrine containing neurons (using tryptophan hydroxylase and dopamine beta-hydroxylase, respectively) was performed. Main Outcome Measures., The UG reflex and cell counts. Results., In saline-injected controls the UG reflex was not evoked in the anesthetized, intact preparation, indicating the presence of the supraspinal inhibition, as previously reported. Injection of anti-SERT saporin into the ventrolateral medulla allowed the UG reflex to be activated in the intact preparation, thus removed the inhibition. This was associated with a decrease in the number of serotonin neurons in the ventrolateral medulla and raphe. No change in the number of noradrenergic neurons was observed. Conclusion., These studies suggest that ventral medullary neurons containing SERT are involved in the tonic inhibition of the UG reflex. Gravitt K, and Marson L. Effect of the destruction of cells containing the serotonin reuptake transporter on urethrogenital Reflexes. J Sex Med 2007;4:322,331. [source] Physiological requirement for the glutamate transporter dEAAT1 at the adult Drosophila neuromuscular junctionDEVELOPMENTAL NEUROBIOLOGY, Issue 10 2006Thomas Rival Abstract L -Glutamate is the major excitatory neurotransmitter in the mammalian brain. Specific proteins, the Na+/K+ -dependent high affinity excitatory amino acid transporters (EAATs), are involved in the extracellular clearance and recycling of this amino acid. Type I synapses of the Drosophila neuromuscular junction (NMJ) similarly use L -glutamate as an excitatory transmitter. However, the localization and function of the only high-affinity glutamate reuptake transporter in Drosophila, dEAAT1, at the NMJ was unknown. Using a specific antibody and transgenic strains, we observed that dEAAT1 is present at the adult, but surprisingly not at embryonic and larval NMJ, suggesting a physiological maturation of the junction during metamorphosis. We found that dEAAT1 is not localized in motor neurons but in glial extensions that closely follow motor axons to the adult NMJ. Inactivation of the dEAAT1 gene by RNA interference generated viable adult flies that were able to walk but were flight-defective. Electrophysiological recordings of the thoracic dorso-lateral NMJ were performed in adult dEAAT1-deficient flies. The lack of dEAAT1 prolonged the duration of the individual responses to motor nerve stimulation and this effect was progressively increased during physiological trains of stimulations. Therefore, glutamate reuptake by glial cells is required to ensure normal activity of the Drosophila NMJ, but only in adult flies. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Hemorrhagic stroke associated with antidepressant use in patients with depression: does degree of serotonin reuptake inhibition matter?PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2009Yan Chen MD Abstract Objective This study aimed to determine whether the degree of serotonin (5-HT) reuptake inhibition affects risk of hemorrhagic stroke associated with antidepressant use in patients with depression. Method A population-based, nested case-control study was performed using a managed care medical claims database. Ninety two depressed patients with a diagnosis of hemorrhagic stroke were identified and matched with 552 controls by age, sex, and year of index date of depression (IDD). Diagnoses of depression, hemorrhagic stroke, and other medical comorbidities were identified using ICD-9 codes. Antidepressants were classified as high, medium, or low reuptake inhibition based on their affinities for the 5-HT reuptake transporter, determined using their respective equilibrium dissociation constants (KD; high: KD,<,1,nM; medium: 1,,,KD,<,10,nM; low: KD,,,10,nM). Conditional logistic regression analysis was performed to estimate the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of the risk of hemorrhagic stroke. Results Compared to non-users of antidepressants, risk of hemorrhagic stroke did not significantly differ between patients who had ever used antidepressants with high (OR,=,0.82; 95% CI,=,0.44,1.55), medium (OR,=,0.93; 95% CI,=,0.37,2.31), or low (OR,=,0.38; 95% CI,=,0.11,1.41) 5-HTT inhibition. Conclusion Risk of hemorrhagic stroke associated with antidepressant use may not be related to an antidepressant's degree of 5-HT reuptake inhibition. Given the limitations of this study, additional studies are needed to confirm these findings. Copyright © 2009 John Wiley & Sons, Ltd. [source] The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case,control study,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Hieronymus J. Derijks PharmD Abstract Purpose Hypoglycaemia is a limiting factor for glycaemic management of diabetes with intensive insulin and/or oral antidiabetic drug (OAD) regimen. Case reports suggest that antidepressants may interfere with blood glucose metabolism in patients with diabetes mellitus potentially increasing the risk of clinically relevant hypoglycaemia. Comorbid depression treated with antidepressants could therefore further complicate glycaemic control. We have carried out a nested case,control study among diabetic patients to assess the risk of hypoglycaemia requiring hospitalisation associated with the use of antidepressants. Methods Diabetic patients treated with insulin and/or OADs were selected from the Dutch Pharmo system. Exposure to antidepressants was the primary determinant investigated. Use of antidepressants was further subclassified based on the receptor binding profile to investigate whether specific pharmacological properties could explain a potential influence on glucose homeostasis. Conditional logistic regression was used to estimate odds ratios and to adjust for confounding factors. Results From the base cohort (40 600 patients), 549 (1.35%) cases were identified and 1897 controls were selected. Current use of any antidepressant was not associated with a significantly higher risk of hypoglycaemia requiring hospitalisation (OR: 1.36 (95%CI: 0.84,2.20)). A trend for a higher risk on hypoglycaemia was identified for antidepressants with high affinity for the serotonin reuptake transporter. The risk on severe hypoglycaemia was increased after 3 years of use (OR: 2.75 (95%CI: 1.31,5.77)). Conclusions It is important for diabetic patients using antidepressants for more than 3 years to pay attention for symptoms of hypoglycaemia and strict blood glucose self-monitoring. Copyright © 2008 John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH,BASIC SCIENCE: Effect of the Destruction of Cells Containing the Serotonin Reuptake Transporter on Urethrogenital ReflexesTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2007Karla Gravitt BSc ABSTRACT Introduction., The urethrogenital (UG) reflex is an autonomic and somatic response that mimics some of the physiological changes seen during ejaculation. The UG reflex is tonically inhibited by neurons in the ventral medulla, an area containing serotonin neurons. Aim., To examine the effect of lesions of brain neurons containing the serotonin reuptake transporter (SERT) on ejaculatory-like reflexes. Methods., Anti-SERT saporin (80 nL, 1 mM) or saline was injected bilaterally into the ventrolateral medulla of male Sprague,Dawley rats. Ten to 18 days later, animals were deeply anesthetized and the presence of the UG reflex was examined before and after acute spinal cord transection (T9,10). Following the experiment the presence and number of serotonin and norepinephrine containing neurons (using tryptophan hydroxylase and dopamine beta-hydroxylase, respectively) was performed. Main Outcome Measures., The UG reflex and cell counts. Results., In saline-injected controls the UG reflex was not evoked in the anesthetized, intact preparation, indicating the presence of the supraspinal inhibition, as previously reported. Injection of anti-SERT saporin into the ventrolateral medulla allowed the UG reflex to be activated in the intact preparation, thus removed the inhibition. This was associated with a decrease in the number of serotonin neurons in the ventrolateral medulla and raphe. No change in the number of noradrenergic neurons was observed. Conclusion., These studies suggest that ventral medullary neurons containing SERT are involved in the tonic inhibition of the UG reflex. Gravitt K, and Marson L. Effect of the destruction of cells containing the serotonin reuptake transporter on urethrogenital Reflexes. J Sex Med 2007;4:322,331. [source] Consequences of Citrobacter rodentium infection on enteroendocrine cells and the enteric nervous system in the mouse colonCELLULAR MICROBIOLOGY, Issue 4 2006Jennifer R. O'Hara Summary We tested the hypothesis that Citrobacter rodentium infection leads to changes in the mucosal enteroendocrine signalling and the enteric nervous system and that the host's immune response contributes to these changes. Enteroendocrine cells, serotonin (5-HT) reuptake transporter (SERT), 5-HT release, and inducible nitric oxide synthase (iNOS) expression were assessed in the colon of infected wild-type or severe combined immunodeficient (SCID) mice. Immunoreactivity for iNOS and neuropeptides were examined in the submucosal and myenteric plexuses. Mice were orogastrically infected with C. rodentium and experiments were conducted during the injury phase (10 days) and the recovery phase (30 days). 5-HT and somatostatin enteroendocrine cells and SERT were significantly reduced 10 days after infection, with numbers returning to control values at 30 days. 5-HT release was increased at 10 days. Changes to the mucosal serotonin signalling system were not observed in SCID mice. iNOS immunoreactivity was increased in the submucosa and mucosa at 10 days and returned to baseline levels by 30 days. No differences were observed in neuropeptide or iNOS immunoreactivity in the enteric plexuses following infection. The host's immune response underlies changes to enteroendocrine cells, SERT expression and 5-HT release in C. rodentium infection. These changes could contribute to disturbances in gut function arising from enteric infection. [source] KETANSERIN-INDUCED BAROREFLEX ENHANCEMENT IN SPONTANEOUSLY HYPERTENSIVE RATS DEPENDS ON CENTRAL 5-HT2A RECEPTORSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007Fu-Ming Shen SUMMARY 1Ketanserin may influence baroreflex function by blocking 5-HT2A receptors and/or ,1 -adrenoceptors through central and/or peripheral mechanisms. 2In the present study, we tested the hypothesis that the baroreflex sensitivity (BRS)-enhancing effects of ketanserin are mediated by central 5-HT2A receptors in spontaneously hypertensive rats (SHR). 3Using a conjugate of a monoclonal antibody to the serotonin reuptake transporter (SERT) and the toxin saporin (anti-SERT-SAP), which specifically eliminates the neurons that express SERT, the effects of ketanserin (0.3 and 3.0 mg/kg, i.g.) on BRS, blood pressure (BP), heart period (HP) and blood pressure variability (BPV) were compared between conscious intact SHR and SHR pretreated with anti-SERT-SAP. 4Immunochemistry showed that, 2 weeks after intracerebroventricular injection of the toxin, 5-HT expression was strikingly attenuated in the brain, whereas values of BRS, BPV and BP were similar to those in the sham group. In intact SHR, 0.3 mg/kg ketanserin significantly improved BRS (191% control) and reduced BPV without affecting BP; at 3.0 mg/kg, ketanserin significantly increased BRS (197% control) and decreased BPV and BP. In toxin-pretreated SHR, only the high dose of ketanserin improved BRS (132% control), neither of the ketanserin doses reduced BPV, but both significantly decreased BP. 5We conclude that the BRS-enhancing effects of ketanserin are mediated largely by central 5-HT2A receptors, whereas the antihypertensive effect of ketanserin persists even after destruction of serotonergic neurons in the central nervous system. [source] ,2 -adrenoceptors are critical for antidepressant treatment of neuropathic pain,ANNALS OF NEUROLOGY, Issue 2 2009Ipek Yalcin PharmD Objective Tricyclic antidepressants (TCAs) are one of the first-line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs. Methods We used pharmacological and genetic approaches in mice to study the role of ARs in the antiallodynic action of the TCA nortriptyline. Peripheral neuropathy was induced by the insertion of a polyethylene cuff around the main branch of the sciatic nerve. The specific role of ,2 -AR was evaluated by studying ,2 -AR,/, mice. We used von Frey filaments to assess mechanical allodynia. Results The antiallodynic action of nortriptyline was not affected by cotreatment with the ,2 -AR antagonist yohimbine, the ,1 -AR antagonists atenolol or metoprolol, or the ,3 -AR antagonist SR 59230A. On the contrary, the ,-AR antagonists propranolol or sotalol, the ,1/,2 -AR antagonists alprenolol or pindolol, or the specific ,2 -AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in ,2 -AR,deficient mice. Interpretation Stimulation of ,2 -AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between ,-blockers that affect ,2 -AR and antidepressant drugs in patients treated for neuropathic pain. Ann Neurol 2009;65:218,225 [source] | |||||||||||||