Mann G E, Zlokovic B V, Yudilevich D L
Biochim Biophys Acta. 1985 Oct 10;819(2):241-8. doi: 10.1016/0005-2736(85)90179-8.
The kinetics and specificity of L-lactate transport into cardiac muscle were studied during a single transit through the isolated perfused rabbit heart using a rapid (15 s) paired-tracer dilution technique. Kinetic experiments revealed that lactate influx was highly stereospecific and saturable with an apparent Kt = 19 +/- 6 mM and a Vmax = 8.4 +/- 1.5 mumol/min per g (mean +/- S.E., n = 14 hearts). At high perfusate concentrations (10 mM), the inhibitors alpha-cyano-4-hydroxycinnamate (Ki = 7.3 mM), pyruvate (Ki = 6.5 mM), acetate (Ki = 19.4 mM) and chloroacetate (Ki = 28 mM) reduced L-lactate influx, and Ki values were estimated assuming a purely competitive interaction of the inhibitors with the monocarboxylate carrier. The monocarboxylic acids [14C]pyruvate and [3H]acetate were themselves transported, and sarcolemmal uptakes of respectively 38 +/- 1% and 70 +/- 8% were measured relative to D-mannitol. Perfusion of hearts for 10-30 min with 0.15 or 1.5 microM glucagon increased myocardial lactate production and simultaneously inhibited tracer uptake of lactate, pyruvate and acetate. It is concluded that a stereospecific lactate transporter exhibiting an affinity for other substituted monocarboxylic acids is operative in the sarcolemmal plasma membrane of the rabbit myocardium.
利用快速(15秒)双示踪剂稀释技术,在离体灌注兔心脏单次通过期间,研究了L-乳酸转运至心肌的动力学和特异性。动力学实验表明,乳酸内流具有高度立体特异性且可饱和,表观Kt = 19±6 mM,Vmax = 8.4±1.5 μmol/(min·g)(均值±标准误,n = 14个心脏)。在高灌注液浓度(10 mM)下,抑制剂α-氰基-4-羟基肉桂酸(Ki = 7.3 mM)、丙酮酸(Ki = 6.5 mM)、乙酸盐(Ki = 19.4 mM)和氯乙酸盐(Ki = 28 mM)降低了L-乳酸内流,并假设抑制剂与单羧酸载体存在纯粹竞争性相互作用来估算Ki值。单羧酸[14C]丙酮酸和[3H]乙酸盐自身也被转运,相对于D-甘露醇,肌膜摄取量分别为38±1%和70±8%。用0.15或1.5 μM胰高血糖素灌注心脏10 - 30分钟,可增加心肌乳酸生成,同时抑制乳酸、丙酮酸和乙酸盐的示踪剂摄取。结论是,一种对其他取代单羧酸具有亲和力的立体特异性乳酸转运体在兔心肌的肌膜质膜中起作用。