Alpha 2-adrenoceptors in the enteric nervous system: a study in alpha 2A-adrenoceptor-deficient mice.
Mammals possess three types of alpha(2)-adrenoceptor, alpha(2A), alpha(2B) and alpha(2C). Our aim was to determine the type of alpha(2)-adrenoceptor involved in the control of gastrointestinal motility. In transmitter overflow experiments, myenteric plexus longitudinal muscle (MPLM) preparations of the ileum were preincubated with [(3)H]-choline and then superfused. The alpha(2)-adrenoceptor agonist medetomidine reduced the electrically evoked overflow of tritium from preparations taken from wild type but not alpha(2A)-adrenoceptor-knockout mice. In a second series of overflow experiments, MPLM preparations were preincubated with [(3)H]-noradrenaline and then superfused. Again medetomidine reduced the electrically evoked overflow of tritium from wild type but not alpha(2A)-knockout preparations. In organ bath experiments, medetomidine reduced electrically evoked contractions of segments of the ileum from wild type but not alpha(2A)-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 alpha(2A)-knockout mice, the speed of gastrointestinal transit was doubled compared to wild-type. Medetomidine, injected intraperitoneally, slowed gastrointestinal transit in wild type but not alpha(2A)-knockout mice. We conclude that the cholinergic motor neurons of the enteric nervous system of mice possess alpha(2)-heteroreceptors which mediate inhibition of acetylcholine release, of neurogenic contractions and of gastrointestinal transit. The noradrenergic axons innervating the intestine possess alpha(2)-autoreceptors. Both hetero- and autoreceptors are exclusively alpha(2A). It is the alpha(2A)-adrenoceptor which in vivo mediates the inhibition of intestinal motility by the sympathetic nervous system.[1]References
- Alpha 2-adrenoceptors in the enteric nervous system: a study in alpha 2A-adrenoceptor-deficient mice. Scheibner, J., Trendelenburg, A.U., Hein, L., Starke, K., Blandizzi, C. Br. J. Pharmacol. (2002) [Pubmed]
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