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-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.
|Autori:||Bellini, M.; Rappelli, L.; Blandizzi, Corrado; Costa, F.; Stasi, C.; Colucci, R.; Giannaccini, Gino; Marazziti, Donatella; Betti, Laura; Baroni, Stefano; Mumolo, M. G.; Marchi, Santino; Del Tacca, Mario|
|Titolo:||Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron|
|Anno del prodotto:||2003|
|Digital Object Identifier (DOI):||10.1016/S0002-9270(03)01702-7|
|Appare nelle tipologie:||1.1 Articolo in rivista|