Role of histamine H3 receptors in control of mouse intestinal motility in vivo and in vitro: comparison with alpha2-adrenoceptors.
We tested drugs acting at histamine H3 receptors in mice on the gastrointestinal transit of a charcoal meal in vivo and on neurogenic contractions of isolated ileal preparations. The agonist (R)-alpha-methylhistamine (100 micromol/kg) caused a maximum 25% reduction of gastrointestinal transit, an effect mimicked by immepip (100 micromol/kg) and antagonized by thioperamide (20 micromol/kg) or clobenpropit (20 micromol/kg). In the isolated ileum, (R)-alpha-methylhistamine (10-100 microM) caused a slight, thioperamide-insensitive, reduction (maximum 15%) of electrically evoked cholinergic contractions. In comparison, the alpha2-adrenoceptor agonist clonidine (0.1 micromol/kg) caused a 35.2% inhibition of the gastrointestinal transit and almost completely reduced (maximum 82% at 1 microM) the cholinergic contraction of the isolated ileum, both effects being antagonized by idazoxan (0.4 micromol/kg and 1 microM, respectively). These results suggest that histamine H3 receptors, located outside the myenteric plexus, mediate an inhibition of the gastrointestinal transit in vivo. Conversely, the presence of a2-adrenoceptors in the cholinergic nerve endings and their inhibitory role in the control of gastrointestinal propulsion is confirmed.
Pozzoli
Cristina
C
University of Parma, School of Medicine, Institute of Pharmacology, Italy.
Todorov
Simeon
S
Schunack
Walter
W
Timmerman
Henk
H
Coruzzi
Gabriella
G
Poli
Enzo
E
D000818:Animals; D002606:Charcoal; D003000:Clonidine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D007082:Ileum / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D051379:Mice; D010528:Peristalsis / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D018100:Receptors, Histamine H3 / Q000502:physiology*
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D010880:Piperidines; D018341:Receptors, Adrenergic, alpha-2; D018100:Receptors, Histamine H3; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D002606:Charcoal; C069357:alpha-methylhistamine; C052075:thioperamide; D003000:Clonidine; D019329:Idazoxan