title: Differential effects of 5-HT3 receptor antagonist on lipid profile in spontaneously hypertensive rat and chromosome 8 congenic strain.
abstract: OBJECTIVE
  Ondansetron is an antagonist of 5-HT3 receptors mostly used as an antiemetic yet known to modulate metabolism and appetite. We tested the metabolic effects of ondansetron in newly derived congenic rat strain, carrying limited chromosome 8 regions of (PD) Brown Norway (BN) and polydactylous (PD) strain origins (including variant serotonin receptor Htr3b gene) within the genomic background of highly inbred model of metabolic syndrome, the spontaneously hypertensive rat (SHR).
  
  
  METHODS
  Adult, standard diet-fed male rats of SHR and the congenic SHR.(PD/BN)8 strains received ondansetron (2mg/kg body weight/day) or vehicle (n=6/strain/treatment) via oral gavage for 14 days while we followed their metabolic and morphometric profiles including glucose tolerance and triacylgycerol and cholesterol concentrations in 20 lipoprotein fractions.
  
  
  RESULTS
  We fine-mapped the chromosome 8 differential segment in the new SHR.(PD/BN)8 congenic strain: it comprises BN-derived region together with an adjacent 422kb stretch of PD origin. The SHR.(PD/BN)8 rats were heavier than SHR, the fasting glucose was significantly higher in ondansetron-treated congenic than in SHR (post-hoc Tukey's HSD p=0.02). Compared to SHR, ondansetron induced significantly more robust increases of cholesterol and triacylglycerol concentrations in total, chylomicron, VLDL and HDL particles in the SHR.(PD/BN)8 congenic strain.
  
  
  CONCLUSIONS
  We established new congenic model with distinct pharmacogenetic profile related to metabolic effects of ondansetron, facilitating thus the search for responsible genetic variants within the limited genomic region demarcated by the differential segment.
authors.affiliation: Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Krupkova
authors.forename: Lucie
authors.initials: L
authors.lastname: Sedova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Liska
authors.forename: Drahomíra
authors.initials: D
authors.lastname: Krenova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kren
authors.forename: Ondrej
authors.initials: O
authors.lastname: Seda
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017294:Ondansetron / Q000494:pharmacology*; D017689:Polydactyly / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*
chemical_list: D008055:Lipids; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D017294:Ondansetron