Monocarboxylate-uptake kinetics in perfused rat heart. 1985

S C Dennis, and M C Kohn, and M B Slegowski, and G J Anderson, and D Garfinkel

While there is considerable evidence to suggest that lactate and pyruvate transport across the cell membrane is controlled, virtually nothing is known about the mechanisms. To test a prediction that sarcolemmal monocarboxylate transport is mediated by a specific carrier, we have examined the kinetics of pyruvate and lactate uptake into aerobically perfused rat hearts. In preparations depleted of intracellular lactate and pyruvate by a 30-min pre-perfusion in the absence of substrates, various concentrations of [14C]lactate or pyruvate (0.02 Ci/mole), together with [3H]mannitol (50 nCi/ml), were transiently (2 min) infused into the mainstream perfusate immediately above the heart. Uptake was calculated from the difference between the level of 14C-labeled substrate predicted from the extracellular distribution of [3H]mannitol and the actual level (corrected for 14CO2 contamination) measured in successive 20-sec samples of effluent perfusate. Computer optimization analysis of the initially rapid (first 60 sec) uptake rates revealed that monocarboxylate transport is not simply a question of diffusion. On the contrary, the observation of typical saturation kinetics (Vmax 7.7-8.4 mumoles/min per g wet wt.) and cross-inhibition (Ki pyr, 2.3 +/- 0.5 mM; Ki lac, 0.16 +/- 0.02 mM) suggest that transsarcolemmal movement of monocarboxylate may be mediated by a high-affinity lactate (km 3.9 +/- 0.9 mM), low-affinity pyruvate (Km 8.6 +/- 1.1 mM), translocase.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007773 Lactates Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
D008297 Male Males
D008353 Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. (L)-Mannitol,Osmitrol,Osmofundin
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D011773 Pyruvates Derivatives of PYRUVIC ACID, including its salts and esters.
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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