α2-adrenoceptors in the enteric nervous system: A study in α2A-adrenoceptor-deficient mice

Abstract

1. 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. 2. 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. 3. 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. 4. In organ bath experiments, medetomidine reduced electrically evoked contractions of segments of the ileum from wild type but not α2A-knockout mice. 5. In each of these three series, phentolamine antagonized the effect of medetomidine in wild-type preparations with greater potency than rauwolscine. 6. 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 wildtype. Medetomidine, injected intraperitoneally, slowed gastrointestinal transit in wild type but not α2A-knockout mice. 7. 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.