Influence of the DA2-receptor agonist quinpirole on the guinea pig ileum

The influence of the dopamine-receptor agonist quinpirole was studied in segments of the guinea pig ileum, mounted to measure longitudinal muscle activity. In concentrations selective for dopamine receptors (10(-9)-10(-7) M), quinpirole did not influence cholinergic twitch responses induced by transmural stimulation at supramaximal voltage, but it concentration-dependently facilitated them in the concentration range 10(-6) to 10(-4) M; the potency of quinpirole was similar to that of metoclopramide (ED50 values, 6.0 x 10(-6) M and 2.2 x 10(-6) M, respectively). Pretreatment of the tissues with 5-hydroxytryptamine or with the 5-hydroxytryptamine receptor antagonists methysergide, ketanserin and R53434 did not influence the facilitatory effect of quinpirole. It was also not influenced by drugs blocking adrenoceptors, dopamine receptors, opioid receptors, muscarinic M1 receptors, GABAA receptors and inhibiting the synthesis of prostaglandins. It was antagonized by the nicotinic receptor antagonist hexamethonium but not by pentolinium. Quinpirole did not enhance contractile responses to acetylcholine and carbachol, but in high concentrations induced contractions in unstimulated preparations. It is concluded that quinpirole facilitates twitch responses in the guinea pig ileum via a prejunctional site of action. This effect is not related to activation of dopamine receptors, but the exact mechanism remains unclear.