Differential peristaltic motor effects of prostanoid (DP, EP, IP, TP) and leukotriene receptor agonists in the guinea-pig isolated small intestine

Abstract

1. Since the role of prostanoid receptors in intestinal peristalsis is largely unknown, the peristaltic motor effects of some prostaglandin (DP, EP, IP), thromboxane (TP) and leukotriene (LT) receptor agonists and antagonists were investigated. 2. Propulsive peristalsis in fluid-perfused segments from the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the intraluminal pressure changes associated with the peristaltic waves. Alterations of distension sensitivity were deduced from alterations of the peristaltic pressure threshold and modifications of peristaltic performance were reflected by modifications of the amplitude, maximal acceleration and residual baseline pressure of the peristaltic waves. 3. Four categories of peristaltic motor effects became apparent: a decrease in distension sensitivity and peristaltic performance as induced by the EP 1/EP 3 receptor agonist sulprostone and the TP receptor agonist U-46,619 (1-1000 nM); a decrease in distension sensitivity without a major change in peristaltic performance as induced by PGD 2 (3-300 nM) and LTD 4 (10-100 nM); a decrease in peristaltic performance without a major change in distension sensitivity as induced by PGE 1, PGE 2 (1-1000 nM) and the EP 1/IP receptor agonist iloprost (1-100 nM); and a decrease in peristaltic performance associated with an increase in distension sensitivity as induced by the EP 2 receptor agonist butaprost (1-1000 nM). The DP receptor agonist BW-245C (1-1000 nM) was without effect. 4. The peristaltic motor action of sulprostone remained unchanged by the EP 1 receptor antagonist SC-51,089 (1 μM) and the DP/EP 1/EP 2 receptor antagonist AH-6809 (30 μM), whereas that of U-46,619 and LTD 4 was prevented by the TP receptor antagonist SQ-29,548 (10 μM) and the cysteinylleukotriene 1 (cysLT 1) receptor antagonist tomelukast (10 μM), respectively. 5. These observations and their pharmacological analysis indicate that activation of EP 2, EP 3, IP, TP and cysLT 1 receptors, but not DP receptors, modulate intestinal peristalsis in a receptor-selective manner, whereas activation of EP 1 seems to be without influence on propulsive peristalsis. In a wider perspective it appears as if the effect of prostanoid receptor agonists to induce diarrhoea is due to their prosecretory but not peristaltic motor action.