Kilbinger H, Kruel R, Pfeuffer-Friederich I, Wessler I
Naunyn Schmiedebergs Arch Pharmacol. 1982 Jun;319(3):231-8. doi: 10.1007/BF00495871.
The effects of metoclopramide on smooth muscle contraction and on release of acetylcholine were studied in the guinea-pig myenteric plexus longitudinal muscle preparation. Acetylcholine was determined either as endogenous acetylcholine, or as labelled transmitter from strips preloaded with 3H-choline. Metoclopramide caused an increase in resting tension of longitudinal muscle as well as an increase in resting output of either endogenous or labelled acetylcholine. Tetrodotoxin abolished the metoclopramide-evoked increase in transmitter release. The increase in smooth muscle tension was clearly related to the increase in resting output. The effects of metoclopramide on both longitudinal muscle contraction and resting release of labelled acetylcholine were prevented in the presence of a concentration of 5-hydroxytryptamine (5-HT) that desensitized 5-HT receptors. This suggests that metoclopramide stimulates neuronal 5-HT receptors and, thereby, facilitates acetylcholine release. Metoclopramide augmented the twitch-like contractions induced by field stimulation at 0.1 Hz. Contractions elicited at 1 Hz were only slightly enhanced. Similarly, metoclopramide facilitated only the release of labelled acetylcholine evoked by electrical stimulation at 0.1 Hz, but not that at 1 Hz. The facilitatory effects of metoclopramide on twitch height and evoked release could not be attributed to a blockade of presynaptic inhibitory alpha-adrenoceptors, dopamine or muscarine receptors.
在豚鼠肠肌丛纵肌标本中研究了甲氧氯普胺对平滑肌收缩及乙酰胆碱释放的影响。乙酰胆碱的测定方式有两种，一种是作为内源性乙酰胆碱，另一种是作为来自预先用3H - 胆碱加载的肌条的标记递质。甲氧氯普胺导致纵肌静息张力增加，同时内源性或标记乙酰胆碱的静息释放量也增加。河豚毒素消除了甲氧氯普胺引起的递质释放增加。平滑肌张力的增加显然与静息释放量的增加有关。在存在使5 - 羟色胺（5 - HT）受体脱敏的5 - HT浓度时，甲氧氯普胺对纵肌收缩及标记乙酰胆碱静息释放的影响均被阻断。这表明甲氧氯普胺刺激神经元5 - HT受体，从而促进乙酰胆碱释放。甲氧氯普胺增强了0.1Hz场刺激诱导的抽搐样收缩。1Hz时诱发的收缩仅略有增强。同样，甲氧氯普胺仅促进0.1Hz电刺激诱发的标记乙酰胆碱释放，而不促进1Hz时的释放。甲氧氯普胺对抽搐高度和诱发释放的促进作用不能归因于对突触前抑制性α - 肾上腺素能受体、多巴胺或毒蕈碱受体的阻断。
