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Am J Physiol Gastrointest Liver Physiol 282: G877-G893, 2002. First published January 9, 2002; doi:10.1152/ajpgi.00435.2001
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Vol. 282, Issue 5, G877-G893, May 2002

5-HT2A receptors: location and functional analysis in intestines of wild-type and 5-HT2A knockout mice

Elena Fiorica-Howells1, Rene Hen2, Jay Gingrich2, Zhishan Li1, and Michael D. Gershon1

Departments of 1 Anatomy and Cell Biology and 2 Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, New York 10032.

The distribution and function of the 5-hydroxytryptamine (5-HT2A) receptor were investigated in the intestines of wild-type (5-HT2A +/+) and knockout (5-HT2A -/-) mice. 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) compared with 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.

serotonin receptors; intestinal motility; immunocytochemistry


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