title: Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron.
abstract: OBJECTIVE
  Serotonin reuptake is mediated by a transporter protein (SERT), and its dysfunctions can alter serotonergic transmission. The present study examines the binding profile of platelet SERT in healthy volunteers as well as in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), both before and after treatment with the 5-HT(3) receptor antagonist alosetron.
  
  
  METHODS
  Binding of [(3)H]paroxetine to SERT was assayed in platelet membranes collected from D-IBS patients (12 women, age 21-73 yr) and healthy volunteers (12 women, age 24-68 yr). Both maximal binding capacity (B(max)) and dissociation constant (K(d)) were estimated. In D-IBS patients, binding parameters and symptom severity score were evaluated at baseline and after treatment with alosetron (1 mg b.i.d. for 8 wk).
  
  
  RESULTS
  At baseline, B(max) and K(d) values of [(3)H]paroxetine binding were respectively lower and higher in D-IBS patients than in healthy volunteers (B(max): 518.7 +/- 155.9 vs 1151.9 +/- 187.4 fmol/mg, p < 0.001; K(d): 0.19 +/- 0.05 vs 0.06 +/- 0.02 nmol/L, p < 0.001). Symptom severity score in D-IBS patients (50.9 +/- 18.8) was negatively correlated with B(max) (r = -0.964; p < 0.001) but not K(d) values (r = -0.164; p = 0.609). After treatment with alosetron, symptom severity score decreased significantly (14.4 +/- 3.7; p < 0.001), whereas B(max) (522.7 +/- 39.7 fmol/mg) and K(d) values (0.17 +/- 0.07 nmol/L) did not change.
  
  
  CONCLUSIONS
  The present results indicate that SERT expressed on platelet membranes of D-IBS patients is characterized by low density and binding affinity and suggest a possible correlation between the reduced capacity of serotonin reuptake and the severity of D-IBS symptoms.
authors.affiliation: Section of Gastroenterology, Department of Internal Medicine, University of Pisa, Ospedale Santa Chiara, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bellini
authors.forename: Lucia
authors.initials: L
authors.lastname: Rappelli
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Costa
authors.forename: Cristina
authors.initials: C
authors.lastname: Stasi
authors.forename: Rocchina
authors.initials: R
authors.lastname: Colucci
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Donatella
authors.initials: D
authors.lastname: Marazziti
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Stefano
authors.initials: S
authors.lastname: Baroni
authors.forename: Maria Gloria
authors.initials: MG
authors.lastname: Mumolo
authors.forename: Santino
authors.initials: S
authors.lastname: Marchi
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets; D002243:Carbolines / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000097:blood*; D003967:Diarrhea / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D008562:Membrane Glycoproteins / Q000097:blood*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins; D018709:Statistics, Nonparametric
chemical_list: D002243:Carbolines; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C090840:alosetron