Lindmar R, Löffelholz K, Weide W
Naunyn Schmiedebergs Arch Pharmacol. 1982 Mar;318(4):295-300. doi: 10.1007/BF00501168.
The efflux of acetylcholine, of radioactively labelled acetylcholine and choline, into the venous effluent of the perfused chicken heart was studied to determine the kinetics of both interstitial washout and hydrolysis of acetylcholine. Stimulation of both cervical vagus nerves (e.g., for 5 s at 40 Hz) caused a release of acetylcholine, which appeared partially unhydrolyzed in the venous effluent, and reduced force of contraction and heart rate. For comparison, labelled acetylcholine or choline was infused for 5 s into the heart and again the venous efflux of either substance was determined. It was found that the kinetics of efflux of acetylcholine or choline from the interstitial space were of first order. The mean half times were 16.2 s (after infusion of acetylcholine) and 17.9 s (after nerve stimulation) for acetylcholine and 17.9 s (after infusion of choline) for choline. In the interstitial space, radioactivity (sum of [3H]-acetylcholine and [3H]-choline formed from [3H]-acetylcholine) released by nerve stimulation declined mono-exponentially with a rate constant of 0.069 s-1 and a half time of 10 s (due to washout), whereas the concentration of unhydrolyzed [3H]-acetylcholine decreased in multi-exponential fashion due to both washout and hydrolysis. The interstitial concentration of [3H]-acetylcholine reached the 50% level after 2.5 s. In conclusion, the long persistence of unhydrolyzed acetylcholine in the interstitial space of the heart appears to be due to an apparently low rate of hydrolysis. This, in turn, is responsible for the importance of diffusion and washout of acetylcholine from the interstitial space as significant factors of synaptic removal of acetylcholine. Moreover, the results support the notion that the sustained interstitial concentration of acetylcholine determines the long duration of cardiac responses to vagal stimulation.
研究了乙酰胆碱、放射性标记的乙酰胆碱和胆碱向灌注鸡心脏静脉流出液中的流出情况，以确定乙酰胆碱的组织间冲洗和水解动力学。刺激双侧颈迷走神经（例如，以40Hz刺激5秒）会导致乙酰胆碱释放，其在静脉流出液中部分未水解，并降低收缩力和心率。为作比较，将标记的乙酰胆碱或胆碱注入心脏5秒，然后再次测定这两种物质的静脉流出情况。结果发现，乙酰胆碱或胆碱从组织间隙的流出动力学符合一级动力学。乙酰胆碱的平均半衰期分别为16.2秒（注入乙酰胆碱后）和17.9秒（神经刺激后），胆碱的平均半衰期为17.9秒（注入胆碱后）。在组织间隙中，神经刺激释放的放射性（[3H]-乙酰胆碱和由[3H]-乙酰胆碱形成的[3H]-胆碱之和）以0.069 s-1的速率常数呈单指数下降，半衰期为10秒（由于冲洗），而未水解的[3H]-乙酰胆碱浓度由于冲洗和水解呈多指数下降。[3H]-乙酰胆碱的组织间隙浓度在2.5秒后达到50%水平。总之，未水解的乙酰胆碱在心脏组织间隙中持续存在的时间较长，这似乎是由于水解速率明显较低。反过来，这又使得乙酰胆碱从组织间隙的扩散和冲洗成为乙酰胆碱突触清除的重要因素。此外，这些结果支持了这样一种观点，即乙酰胆碱在组织间隙中的持续浓度决定了心脏对迷走神经刺激反应的持续时间。
