Reduction of gastrointestinal serotonin in alloxan-diabetic rats: reversal by 5-hydroxytryptophan treatment.

A rat model of alloxan-induced diabetes was used to investigate the effect of diabetic state on serotonin (5-HT) levels in peripheral body compartments, gastrointestinal (GI) and platelet, and the metabolic response of these compartments to serotonin precursor (5-hydroxytryptophan, 5-HTP) loading in diabetes. In all segments of diabetic gut a massive reduction in 5-HT concentration (to 45-64% at 6th week after induction of diabetes, with further progression to 30-52% at 14th week) was shown. After parenteral loading with 5-HTP for 6 days (30 mg/kg per day) 5-HT concentration in all parts of the GI tract returned to the control values (82-108%), indicating reduced serotonin precursor availability in diabetes. Platelet serotonin levels (PSL) in diabetic rats demonstrated a slight gradual reduction that became significant at 14th week of diabetic state. On the mentioned 5-HTP challenge only blunted response of PSL in diabetics, as contrasted to control animals (54% vs. 113%) was shown, indicating possible suppression of the membrane 5-HT transporter. The observed alterations in peripheral 5-HT homeostasis in diabetic rats as well as the possibility of their reversal by 5-HTP treatment could be of clinical interest.