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.
Scheibner
Jens
J
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Freiburg, Albert-Strasse 25, D-79104 Freiburg i.Br., Germany. scheibne@uni-freiburg.de
Trendelenburg
Anne-Ulrike
AU
Hein
Lutz
L
Starke
Klaus
K
Blandizzi
Corrado
C
D000109:Acetylcholine / Q000378:metabolism; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D017615:Enteric Nervous System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency* / Q000235:genetics*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D000109:Acetylcholine; D009638:Norepinephrine