Endogenous 5‐HT2B receptor activation regulates neonatal respiratory activity in vitro

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Abstract
An implication of 5‐HT2B receptors in central nervous system has not yet been clearly elucidated. We studied the role of different 5‐HT2 receptor subtypes in the medullary breathing center, the pre‐Bötzinger complex, and on hypoglossal motoneurons in rhythmically active transversal slice preparations of neonatal rats and mice. Local microinjection of 5‐HT2 receptor agonists revealed tonic excitation of hypoglossal motoneurons. Excitatory effects of the 5‐HT2B receptor agonist BW723C86 could be blocked by bath application of LY272015, a highly selective 5‐HT2B receptor antagonist. Excitatory effects of the 5‐HT2A/B/C receptor agonist α‐methyl 5‐HT could be blocked by the preferential 5‐HT2A receptor antagonist ketanserin. Therefore, 5‐HT‐induced excitation of hypoglossal motoneurons is mediated by convergent activation of 5‐HT2A and 5‐HT2B receptors. Local microinjection of BW723C86 in the pre‐Bötzinger complex increased respiratory frequency. Bath application of LY272015 blocked respiratory activity, whereas ketanserin had no effect. Therefore, endogenous 5‐HT appears to support tonic action on respiratory rhythm generation via 5‐HT2B receptors. In preparations of 5‐HT2B receptor‐deficient mice, respiratory activity appeared unaltered. Whereas BW723C86 and LY272015 had no effects, bath application of ketanserin disturbed and blocked rhythmic activity. This demonstrates a stimulatory role of endogenous 5‐HT2B receptor activation at the pre‐Bötzinger complex and hypoglossal motoneurons that can be taken up by 5‐HT2A receptors in the absence of 5‐HT2B receptors. The presence of functional 5‐HT2B receptors in the neonatal medullary breathing center indicates a potential convergent regulatory role of 5‐HT2B and ‐2A receptors on the central respiratory network. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006