Expression and function of 5-HT3receptors in the enteric neurons of mice lacking the serotonin transporter

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Abstract
The actions of enteric 5-HT are terminated by 5-HT transporter (SERT)-mediated uptake, and gastrointestinal motility is abnormal in SERT −/− mice. We tested the hypothesis that adaptive changes in enteric 5-HT3receptors help SERT −/− mice survive despite inefficient 5-HT inactivation. Expression of mRNA encoding enteric 5-HT3Asubunits was similar in SERT +/+ and −/− mice, but that of 5-HT3Bsubunits was fourfold less in SERT −/− mice. 5-HT3BmRNA was found, by in situ hybridization, in epithelial cells and enteric neurons. 5-HT evoked a fast inward current in myenteric neurons that was pharmacologically identified as 5-HT3mediated. The EC50of the 5-HT response was lower in SERT +/+ (18 μM) than in SERT −/− (36 μM) mice and desensitized rapidly in a greater proportion of SERT −/− neurons; however, peak amplitudes, steady-state current, and decay time constants were not different. Adaptive changes thus occur in the subunit composition of enteric 5-HT3receptors of SERT −/− mice that are reflected in 5-HT3receptor affinity and desensitization.