Pinz Ilka, Pörtner Hans-O
Alfred-Wegener-Institute for Polar and Marine Research, 27568 Bremerhaven, Germany.
J Appl Physiol (1985). 2003 Mar;94(3):1177-85. doi: 10.1152/japplphysiol.00131.2002. Epub 2002 Nov 8.
The mechanism of an increase in metabolic rate induced by lactate was investigated in the toad Bufo marinus. Oxygen consumption (Vo(2)) was analyzed in fully aerobic animals under hypoxic conditions (7% O(2) in air), accompanied by measurements of catecholamines in the plasma, and was measured in isolated hepatocytes in vitro under normoxia by using specific inhibitors of lactate proton symport [alpha-cyano-4-hydroxycinnamate (CHC)] and sodium proton exchange (EIPA). The rise in metabolic rate in vivo can be elicited by infusions of hyperosmotic (previous findings) or isosmotic sodium lactate solutions (this study). Despite previous findings of reduced metabolic stimulation under the effect of adrenergic blockers, the increase in Vo(2) in vivo was not associated with elevated plasma catecholamine levels, suggesting local release and effect. In addition to the possible in vivo effect via catecholamines, lactate induced a rise in Vo(2) of isolated hepatocytes, depending on the concentration present in a weakly buffered Ringer solution at pH 7.0. No increase was found at higher pH values (7.4 or 7.8) or in HEPES-buffered Ringer solution. Inhibition of the Lac(-)-H(+) transporter with alpha-CHC or of the Na(+)/H(+) exchanger with EIPA prevented the increase in metabolic rate. We conclude that increased Vo(2) at an elevated systemic lactate level may involve catecholamine action, but it is also caused by an increased energy demand of cellular acid-base regulation via stimulation of Na(+)/H(+) exchange and thereby Na(+)-K(+)-ATPase. The effect depends on entry of lactic acid into the cells via lactate proton symport, which is likely favored by low cellular surface pH. We suggest that these energetic costs should also be considered in other physiological phenomena, e.g., when lactate is present during excess, postexercise Vo(2).
在海蟾蜍（Bufo marinus）中研究了乳酸诱导代谢率增加的机制。在低氧条件下（空气中含7% O₂）对完全有氧的动物的耗氧量（Vo₂）进行分析，同时测定血浆中的儿茶酚胺，并在常氧条件下使用乳酸质子同向转运体[α-氰基-4-羟基肉桂酸（CHC）]和钠质子交换（EIPA）的特异性抑制剂在体外分离的肝细胞中进行测量。体内代谢率的升高可通过输注高渗（先前的研究结果）或等渗乳酸钠溶液（本研究）引发。尽管先前有研究发现肾上腺素能阻滞剂作用下代谢刺激减弱，但体内Vo₂的增加与血浆儿茶酚胺水平升高无关，提示存在局部释放和作用。除了通过儿茶酚胺可能产生的体内效应外，乳酸还会使分离的肝细胞的Vo₂升高，这取决于pH值为7.0的弱缓冲林格溶液中乳酸的浓度。在较高pH值（7.4或7.8）或HEPES缓冲林格溶液中未发现增加。用α-CHC抑制Lac⁻-H⁺转运体或用EIPA抑制Na⁺/H⁺交换体可防止代谢率升高。我们得出结论，全身乳酸水平升高时Vo₂的增加可能涉及儿茶酚胺的作用，但它也是通过刺激Na⁺/H⁺交换从而激活Na⁺-K⁺-ATPase，导致细胞酸碱调节的能量需求增加所引起的。这种效应取决于乳酸通过乳酸质子同向转运进入细胞，而低细胞表面pH可能有利于这种转运。我们建议在其他生理现象中也应考虑这些能量消耗，例如，运动后过量乳酸存在时的Vo₂情况。
