Role of histamine H3 receptors in control of mouse intestinal motility in vivo and in vitro: comparison with alpha2-adrenoceptors |
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Authors: | Pozzoli Cristina Todorov Simeon Schunack Walter Timmerman Henk Coruzzi Gabriella Poli Enzo |
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Institution: | (1) School of Medicine, Institute of Pharmacology, University of Parma, Parma, Italy;(2) Bulgarian Academy of Sciences, Department of Physiology, Academy G. Bonchev Sofia, Sofia, Bulgaria;(3) Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany;(4) Centre Leiden/Amsterdam for Drug Research, Vrjie Universiteit, Amsterdam, The Netherlands |
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Abstract: | 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)- -methylhistamine (100 mol/kg) caused a maximum 25% reduction of gastrointestinal transit, an effect mimicked by immepip (100 mol/kg) and antagonized by thioperamide (20 mol/kg) or clobenpropit (20 mol/kg). In the isolated ileum, (R)- -methylhistamine (10–100 M) caused a slight, thioperamide-insensitive, reduction (maximum 15%) of electrically evoked cholinergic contractions. In comparison, the 2-adrenoceptor agonist clonidine (0.1 mol/kg) caused a 35.2% inhibition of the gastrointestinal transit and almost completely reduced (maximum 82% at 1 M) the cholinergic contraction of the isolated ileum, both effects being antagonized by idazoxan (0.4 mol/kg and 1 M, 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 2-adrenoceptors in the cholinergic nerve endings and their inhibitory role in the control of gastrointestinal propulsion is confirmed. |
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Keywords: | histamine H3 receptors 2-adrenoceptors" target="_blank">gif" alt="agr" align="BASELINE" BORDER="0">2-adrenoceptors gastrointestinal transit mouse |
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