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Am J Physiol Gastrointest Liver Physiol (September 4, 2002). doi:10.1152/ajpgi.00203.2002
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Articles in PresS, published online ahead of print September 4, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00203.2002
Submitted on May 29, 2002
Accepted on August 9, 2002

Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter

Min-tsai Liu1*, Stephen Rayport2, Yan Jiang1, Dennis L. Murphy3, and Michael D. Gershon1

1 Department of Anatomy and Cell Biology, Columbia University, New York, New York, USA
2 Department of Anatomy and Cell Biology, Columbia University, New York, New York, USA; Department of Neuroscience, NYS Psychiatric Institute, New York, New York, USA
3 Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland, USA

* To whom correspondence should be addressed. E-mail: ml27{at}columbia.edu.

The actions of enteric 5-HT are terminated by SERT-mediated uptake and gastrointestinal motility is abnormal in SERT -/-mice. We tested the hypothesis that adaptive changes in enteric 5-HT3 receptors help SERT -/- mice survive despite inefficient 5-HT inactivation. Expression of mRNA encoding enteric 5-HT3A subunits was similar in SERT+/+ and -/- mice, but that of 5-HT3B subunits was 4-fold less in SERT -/- mice. 5-HT3B mRNA 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-HT3-mediated. The EC50 of the 5-HT response was lower in SERT +/+ (18 µM) than in -/- (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-HT3 receptors of SERT-/- mice that are reflected in 5-HT3 receptors affinity and desensitization.




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