Histamine H3 receptors do not modulate reflex-evoked peristaltic motility in the isolated guinea-pig ileum.

We investigated the role played by histamine H3 receptors in the control of intestinal peristalsis, using two different in vitro preparations of guinea-pig ileum. (a) Ileal segments were perfused from the oral end, inducing peristaltic movements (emptying waves), due to the activation of intramural reflexes. Such peristaltic motility was measured as changes in the perfusion pressure during the emptying phase and the threshold pressure for triggering the emptying wave was determined. (b) Ileal segments were mounted horizontally and circular muscle contraction evoked by the ascending peristaltic reflex was triggered by caudal distension of the intestinal wall. In perfused ileal segments, specific agonists acting at histamine H3 receptors, ((R)-alpha-methylhistamine and immepip, 1 nmol-10 micromol/l), did not cause any change in the threshold pressure for triggering the peristaltic wave, or in the rise of the perfusion pressure during the emptying phase. Similarly, circular muscle contractions evoked by caudal distension of the wall were not affected by these histamine H3 receptor agonists up to 10 micromol/l. In the same conditions, a complete inhibition of peristaltic movements was elicited by agonists acting at alpha2-adrenoceptors or adenosine A1 receptors (compound UK 14,304 and N6-cyclopentyladenosine, respectively), their effects being prevented by the respective receptor antagonists, idazoxan and 8-cyclopentyl-1,3-dimethyl-xanthine. These data demonstrate that, contrary to alpha2-adrenoceptors and adenosine A1 receptors, histamine H3 receptors are not primarily involved in the modulation of intramural reflexes that modulate the peristaltic motility of the isolated guinea-pig ileum.