体内刺激离体鸡心脏和大鼠皮层中的毒蕈碱受体对细胞胆碱的动员作用。

Mobilization of cellular choline by stimulation of muscarine receptors in isolated chicken heart and rat cortex in vivo.

作者信息

Corradetti R, Lindmar R, Löffelholz K

出版信息

J Pharmacol Exp Ther. 1983 Sep;226(3):826-32.

Abstract

The effects of cholinesterase inhibitors and muscarinic agonists on efflux of choline were studied in isolated perfused chicken heart and rat cortex in vivo. In the heart, the phospholipase A2 inhibitor mepacrine (10(-4) M) reduced the choline efflux (1.1 nmol g-1 min-1) by 51 +/- 5% (N = 3), whereas several cholinesterase inhibitors (physostigmine, neostigmine and diisopropylfluorophosphate) and muscarinic agonists (acetylcholine, oxotremorine and bethanechol) caused an increase. The muscarinic increase in choline efflux appears to be specific, as the increase caused by 10(-6) M physostigmine (+113%), by 3 X 10(-7) M acetylcholine (+89%) or by 5 X 10(-4) M bethanechol (+29%) was blocked by atropine. Cholinesterase inhibitors and muscarinic agonists also caused a decrease in heart rate by about 50%. Papaverine (10(-5) M) blocked the physostigmine- or bethanechol-evoked increase in choline efflux, but left the decrease in heart rate unchanged. Choline efflux from rat cortex in vivo was studied using the "cup technique." During the experimental period (3 hr), resting efflux declined from 60 to 15 pmol cm-2 min-1. Again choline efflux was increased by physostigmine (+48%) or by bethanechol (+48%) added to the cup solution from 80 to 160 min, whereas a decrease was observed after atropine plus physostigmine (-36%) or atropine plus bethanechol (-26%). In conclusion, stimulation of muscarine receptors increased extracellular choline by mobilization of cellular choline presumably through an effect on phospholipid metabolism. The hypothesis is discussed that synthesis of acetylcholine in the brain may be supported by an autoregulation of precursor availability.

摘要

在离体灌注鸡心脏和大鼠大脑皮层活体中研究了胆碱酯酶抑制剂和毒蕈碱激动剂对胆碱流出的影响。在心脏中，磷脂酶A2抑制剂米帕林（10⁻⁴ M）使胆碱流出量（1.1 nmol g⁻¹ min⁻¹）降低了51±5%（N = 3），而几种胆碱酯酶抑制剂（毒扁豆碱、新斯的明和二异丙基氟磷酸酯）以及毒蕈碱激动剂（乙酰胆碱、氧化震颤素和氨甲酰甲胆碱）则使其增加。毒蕈碱引起的胆碱流出增加似乎具有特异性，因为10⁻⁶ M毒扁豆碱（增加113%）、3×10⁻⁷ M乙酰胆碱（增加89%）或5×10⁻⁴ M氨甲酰甲胆碱（增加29%）引起的增加被阿托品阻断。胆碱酯酶抑制剂和毒蕈碱激动剂还使心率降低了约50%。罂粟碱（10⁻⁵ M）阻断了毒扁豆碱或氨甲酰甲胆碱引起的胆碱流出增加，但心率降低未变。使用“杯技术”研究了大鼠大脑皮层活体中的胆碱流出。在实验期间（3小时），静息流出量从60下降至15 pmol cm⁻² min⁻¹。同样，在80至160分钟时，添加到杯溶液中的毒扁豆碱（增加48%）或氨甲酰甲胆碱（增加48%）使胆碱流出增加，而阿托品加毒扁豆碱（降低36%）或阿托品加氨甲酰甲胆碱（降低26%）后则观察到流出减少。总之，毒蕈碱受体的刺激可能通过对磷脂代谢的影响，动员细胞内胆碱从而增加细胞外胆碱。讨论了这样一种假说，即大脑中乙酰胆碱的合成可能受到前体可用性自动调节的支持。