Abstract
It is known that tachykinins (substance P, neurokinin A) participate in the excitatory neural pathways subserving peristaltic motor activity in the intestine. The aim of the present study was to elucidate the types of tachykinin receptor (NK-1 or NK-2) involved in peristalsis by the use of receptor subtype-selective antagonists. Peristaltic motility in isolated segments of the guinea-pig ileum was induced by pumping fluid into the oral end of the intestinal segment. By way of the intraluminal pressure the compliance of the intestinal wall during the preparatory phase and the pressure threshold to trigger the emptying phase of peristalsis were recorded. The tachykinin antagonists were used at concentrations that were at least 30 times in excess of the equilibrium dissociation constants which had previously been evaluated with receptor subtype-selective agonists on the guineapig ileum circular muscle. The NK-1 selective antagonist CP-96,345 (0.3 μM) had a slight stimulant influence on peristalsis, whereas the NK-2 selective antagonists MEN-10,376 (10 μM), GR-94,800 (0.3 μM) and SR-48,968 (0.1 μM) led to a small inhibition of motor activity. However, when given after exposure of the ileum to a threshold concentration of atropine (5–20 nM) causing little depression of peristalsis, the tachykinin NK-2 receptor antagonists invariably abolished peristalsis. This synergistic interaction was not seen when SR-48,968 was administered after the ileal segments had been exposed to concentrations of hexamethonium, isoproterenol or calcitonin gene-related peptide that by themselves caused a slight inhibition of peristalsis only. CP-96,345 was without effect on peristalsis when it was applied in the presence of a threshold concentration of atropine. These findings indicate that transmission via tachykinin NK-2, but not NK-1, receptors synergizes with cholinergic transmission via muscarinic receptors in the relay of excitatory enteric pathways subserving intestinal peristalsis.
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Correspondence to: P. Holzer at the above address
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Holzer, P., Maggi, C.A. Synergistic role of muscarinic acetylcholine and tachykinin NK-2 receptors in intestinal peristalsis. Naunyn-Schmiedeberg's Arch Pharmacol 349, 194–201 (1994). https://doi.org/10.1007/BF00169837
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DOI: https://doi.org/10.1007/BF00169837