α2 -Adrenoceptors in the enteric nervous system: a study in α2A -adrenoceptor-deficient mice

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Abstract
Mammals possess three types of α2‐adrenoceptor, α2A, α2B and α2C. Our aim was to determine the type of α2‐adrenoceptor involved in the control of gastrointestinal motility. In transmitter overflow experiments, myenteric plexus longitudinal muscle (MPLM) preparations of the ileum were preincubated with [3H]‐choline and then superfused. The α2‐adrenoceptor agonist medetomidine reduced the electrically evoked overflow of tritium from preparations taken from wild type but not α2A‐adrenoceptor‐knockout mice. In a second series of overflow experiments, MPLM preparations were preincubated with [3H]‐noradrenaline and then superfused. Again medetomidine reduced the electrically evoked overflow of tritium from wild type but not α2A‐knockout preparations. In organ bath experiments, medetomidine reduced electrically evoked contractions of segments of the ileum from wild type but not α2A‐knockout mice. In each of these three series, phentolamine antagonized the effect of medetomidine in wild‐type preparations with greater potency than rauwolscine. In conscious mice, gastrointestinal transit was assessed by means of an intragastric charcoal bolus. In α2A‐knockout mice, the speed of gastrointestinal transit was doubled compared to wild‐type. Medetomidine, injected intraperitoneally, slowed gastrointestinal transit in wild type but not α2A‐knockout mice. We conclude that the cholinergic motor neurons of the enteric nervous system of mice possess α2‐heteroreceptors which mediate inhibition of acetylcholine release, of neurogenic contractions and of gastrointestinal transit. The noradrenergic axons innervating the intestine possess α2‐autoreceptors. Both hetero‐ and autoreceptors are exclusively α2A. It is the α2A‐adrenoceptor which in vivo mediates the inhibition of intestinal motility by the sympathetic nervous system. British Journal of Pharmacology (2002) 135, 697–704; doi:10.1038/sj.bjp.0704512