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Articles in PresS, published online ahead of print January 9, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00435.2001
Submitted on October 11, 2001
Accepted on January 7, 2002
1 Anatomy & Cell Biology, Columbia University, College of Physicians & Surgeons, New York, New York, USA
2 Pharmacology, Columbia University, College of Physicians & Surgeons, New York, New York, USA
3 Psychiatry, New York State Psychiatric Institute, New York, New York, USA
* To whom correspondence should be addressed. E-mail: ef7{at}columbia.edu.
The distribution and function of the 5-HT2A receptor were investigated in the intestines of wild-type (5-HT2A +/+) and knockout mice (5-HT2A -/-). In 5-HT2A +/+ mice, rats, and guinea pigs, 5-HT2A receptor immunoreactivity was found on circular and longitudinal smooth muscle cells, neurons, enterocytes, and Paneth cells. Muscular 5-HT2A receptors were concentrated in caveolae; neuronal 5-HT2A receptors were found intracellularly and on the plasma membranes of nerve cell bodies and axons. Neuronal 5-HT2A immunoreactivity was detected as early as E14 in ganglia, intravillus nerves, and the deep muscle plexus. The 5-HT2A -/- colon did not express 5-HT2A receptors and did not contract in response to exogenous 5-HT. 5-HT2A -/- enterocytes were smaller, Paneth cells fewer, and muscle layers thinner (and showed degeneration) than those of 5-HT2A +/+ littermates. The 5-HT2A receptor may thus be required for the maintenance and/or development of enteric neuroeffectors and other enteric functions, although gastrointestinal and colonic transit times in 5-HT2A -/- and +/+ mice did not differ significantly.
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