Acara M, Rennick B
J Pharmacol Exp Ther. 1976 Oct;199(1):32-40.
The renal excretion of 14C-choline or 14C-acetylcholine was increased by the infusion of another organic cation at low rates but was decreased by infusion of the same added organic cation at higher rates with the Sperber technique in hens. The range of low rates of infusion was from 1 X 10(-15) to 1 X 10(-8) mol/min. At infusion rates greater than 1 X 10(-8) mol/min, inhibition of tubular excretion was found. At the low infusion rates, thiamine, lysine, quinine, atropine, acetylcholine and methylguanidine were found to increase 14C-choline excretion. The same compounds with the exception of lysine and acetylcholine inhibited 14C-choline excretion at the higher infusion rates. A biphasic effect on 14C-acetylcholine excretion was also observed with added atropine, thiamine and choline over the same infusion range. Increases in 14C-choline excretion occurred during a choline infusion rate that normally produced an excretory tubular maximum for choline whereas increases in 14C-acetylcholine excretion occurred during infusion of tracer amounts of 14C-acetylcholine. The effect of the addition of organic cations was selective for cations since the tubular excretion of organic anions was not affected by the addition of organic cations. The tubular excretion ratio of 14C-thiamine/p-aminohippuric acid increased from 0.25 to 0.95 when the infusion rate of added unlabeled thiamine was increased from 1 X 10(-11) to 1 X 10(-8) mol/min. Enhanced tubular excretion of 14C-thiamine may represent the effect of the increased load of unlabeled thiamine to protect the labeled thiamine from conversion to a nontransportable metabolite. Enhancement of excretion of 14C-choline and 14C-acetyocholine produced by very small amounts of other organic cations may represent either inhibition of tubular reabsorptive transport or induction of tubular excretory transport.
采用斯珀伯技术,在母鸡体内以低速率输注另一种有机阳离子会增加14C-胆碱或14C-乙酰胆碱的肾排泄,但以较高速率输注相同的添加有机阳离子时则会使其肾排泄减少。低输注速率范围为1×10(-15)至1×10(-8)摩尔/分钟。当输注速率大于1×10(-8)摩尔/分钟时,发现肾小管排泄受到抑制。在低输注速率下,发现硫胺素、赖氨酸、奎宁、阿托品、乙酰胆碱和甲基胍会增加14C-胆碱的排泄。除赖氨酸和乙酰胆碱外,相同的化合物在较高输注速率下会抑制14C-胆碱的排泄。在相同的输注范围内,添加阿托品、硫胺素和胆碱对14C-乙酰胆碱排泄也观察到双相效应。在胆碱输注速率通常产生胆碱排泄肾小管最大值期间,14C-胆碱排泄增加,而在输注示踪量的14C-乙酰胆碱期间,14C-乙酰胆碱排泄增加。添加有机阳离子的作用对阳离子具有选择性,因为有机阴离子的肾小管排泄不受添加有机阳离子的影响。当未标记硫胺素的输注速率从1×10(-11)增加到1×10(-8)摩尔/分钟时,14C-硫胺素/对氨基马尿酸的肾小管排泄率从0.25增加到0.95。14C-硫胺素肾小管排泄增强可能代表未标记硫胺素负荷增加的作用,以保护标记硫胺素不转化为不可转运的代谢物。极少量其他有机阳离子产生的14C-胆碱和14C-乙酰胆碱排泄增强可能代表肾小管重吸收转运的抑制或肾小管排泄转运的诱导。