Guenaneche F, Lefebvre R A
Heymans Institute of Pharmacology, University of Gent Medical School, Belgium.
J Pharmacol Exp Ther. 1990 Aug;254(2):489-95.
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.
研究了多巴胺受体激动剂喹吡罗对豚鼠回肠节段的影响，该回肠节段被安装用于测量纵肌活动。在对多巴胺受体具有选择性的浓度（10⁻⁹ - 10⁻⁷M）下，喹吡罗不影响由超最大电压的跨壁刺激诱导的胆碱能抽搐反应，但在10⁻⁶至10⁻⁴M的浓度范围内，它以浓度依赖性方式促进这些反应；喹吡罗的效力与甲氧氯普胺相似（ED50值分别为6.0×10⁻⁶M和2.2×10⁻⁶M）。用5-羟色胺或5-羟色胺受体拮抗剂麦角新碱、酮色林和R53434对组织进行预处理，不影响喹吡罗的促进作用。它也不受阻断肾上腺素能受体、多巴胺受体、阿片受体、毒蕈碱M1受体、GABAA受体以及抑制前列腺素合成的药物的影响。它被烟碱受体拮抗剂六甲铵拮抗，但不被潘托铵拮抗。喹吡罗不增强对乙酰胆碱和卡巴胆碱的收缩反应，但在高浓度下可诱导未刺激制剂的收缩。得出的结论是，喹吡罗通过节前作用位点促进豚鼠回肠的抽搐反应。这种作用与多巴胺受体的激活无关，但确切机制仍不清楚。
