Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron

Bellini, Massimo; Rappelli, Lucia; Blandizzi, Corrado; Costa, Francesco; Stasi, Cristina; Colucci, Rocchina; Giannaccini, Gino; Marazziti, Donatella; Betti, Laura; Baroni, Stefano; Mumolo, Maria Gloria; Marchi, Santino; Del Tacca, Mario
December 2003
American Journal of Gastroenterology;Dec2003, Vol. 98 Issue 12, p2705
Academic Journal
OBJECTIVES: 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-HT3 receptor antagonist alosetron. METHODS: Binding of [³H]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 (Bmax) and dissociation constant (Kd) 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, Bmax and Kd values of [³H]paroxetine binding were respectively lower and higher in D-IBS patients than in healthy volunteers (Bmax: 518.7 ± 155.9 vs 1151.9 ± 187.4 nmol/mg, p < 0.001; Kd: 0.19 ± 0.05 vs 0.06 ± 0.02 nmol/L, p < 0.00 1). Symptom severity score in D-IBS patients (50.9 ± 18.8) was negatively correlated with Brnax (r = -0.964; p < 0.001) but not Kd values (r = -0.164; p = 0.609). After treatment with alosetron, symptom severity score decreased significantly (14.4 ± 3.7; p < 0.00 1), whereas Brnax (522.7 ± 39.7 nmol/mg) and Kd 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.


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