Browsing by Subject "5-HT3 receptors"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Elucidation of Mechanism and Molecular Determinants Important in Picrotoxin Action in the 5-Hydroxytryptamine Type 3 Receptor(2003-09-01) Das, Paromita; Basu, Alakananda; Forster, Michael J.; Luedtke, Robert R.Das, Paromita, Elucidation of mechanism and molecular determinants important in picrotoxin action in the 5-hydroxytryptamin type 3 receptor. Doctor of Philosophy (Pharmacology and Neuroscience), September 2003, pp. 192, 3 tables, 26 illustrations, 67 titles. The 5-HT3 receptor belongs to the superfamily of ligand-gated ion channels (LGIC), which mediate fast neurotransmission. Till date, only two subtypes of the receptor i.e. 5-HT3A and 5-HT3B have been investigated. The GABAA receptor antagonist picrotoxin inhibits other anion-selective members of the LGIC. Whether PTX inhibits the cation-selective 5-HT3 receptors was previously unknown. Thus, the primary goal of this study was to elucidate the mechanism of action of PTX and identify the amino acids involved in the action of PTX in 5-HT3 receptors. The overall hypothesis tested was that PTX inhibits the 5-HT3 receptor by interacting in the ion channel. PTX-mediated blockade of the 5-HT3A receptors was non-competitive and use-facilitated similar to GABAA receptors suggesting a conserved site of action of these ligands. The inhibitory effect of PTX was reduced drastically in heteromeric 5-HT3A/3B receptors, compared to homomeric 5-HT3A receptors. Picrotoxin should prove to be a useful probe for determining the presence of homomeric vs. heteromeric 5-HT3 receptors in native tissue and recombinant receptor preparations. In anion-selective ion channels, the 2’, 3’ and 6’resides in cytoplasmic aspect of TM2 are known to modulate PTX sensitivity. While mutation of 2’ and 3’ residues in 5-dramatic loss of sensitivity to PTX in 5-HT3A receptors. A converse mutation at 6’ residue in the 5-HT3B subunit caused gain of sensitivity to PTX, suggesting that 6’ is a key determinant of PTX sensitivity. A novel finding was the involvement of 7’ residue in increasing PTX sensitivity in 5-HT3A but not the 5-HT3B subunit. The lack of specific binding by radioligand [3H]EBOB in 5-HT3A receptors suggested that the site of action of convulsants may be different from that anion-selective receptors. The overall results suggest that PTX interacts from that in the anion-selective receptors. The overall results suggest that PTX interact in the ion channel in the 5-HT3 receptors but also underscores the complexity of its interaction with LGICs.Item The Effectiveness of Outpatient Antiemetic for Patients on Platinum, Camptosar, and Anthracycline-Based Chemotherapy(2002-07-25) Wiggins, Jenny Marie; Victoria Rudick; Julie PrejeanAbstract. Chemotherapy-induced nausea and vomiting (CINV) is a serious problem affecting at least 50% of patients. Some nausea and vomit pathways involve serotonin and serotonin type-3 (5-HT3) receptors for propagation of the reflex. 5-HT3 antagonists were developed to block the 5-HT3 receptors and inhibit emesis. Anzemet, Kytril, and Zofran are 5-HT3 antagonists used as antiemetics in patients receiving emetogenic chemotherapy. This study was designed to determine if current antiemetic therapy involving these 5-HT3 antagonists is effective for patents on platinum, camptosar, and anthracycline-based chemotherapy. The data from this study could be used to assert or adjust antiemetic therapy in patients on these chemotherapy regimens, thus providing better quality of life for patients as they undergo chemotherapy. Patients on platinum, camptosar, or anthracycline-based chemotherapies from three Fort Worth area clinics of Texas Cancer Care were chosen to gauge the effectiveness of their antiemetic regimen based on chemotherapy regimen, patient compliance, and specific 5-HT3 antagonist. Data was gathered based on questionnaires filled out by the patient for seven days and their chemotherapy nurse on the day of their treatment. It was found that Zofran was the 5-HT3 antagonist most often prescribed by the nurses. Patient compliance was not a factor in patient perception of CINV, because of the high levels of patient cooperation. Each of the chemotherapy regimens differed by day in overall average level of CINV. Patients on Kytril were found to experience more “severe” CINV than those taking Anzemet or those not taking a 5-HT3 antagonist as an outpatient. A recommendation from this study would be a larger sample size and a larger span of time. Each of the study sites should also be compared for nurse prescribing habits and patient compliance, as well as a higher level of decadron usage for patients experiencing moderate and severe CINV.