Kinetics of Adenosine Uptake by Erythrocytes, and the Influence of Dipyridamole

• Published in: Molecular pharmacology Vol. 8; no. 4; pp. 417 - 425
• Main Authors: Roos, H, Pfleger, K
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.07.1972
• Subjects: Adenosine - antagonists & inhibitors; Adenosine - blood; Adenosine - metabolism; Animals; Carbon Isotopes; Depression, Chemical; Diffusion; Dipyridamole - pharmacology; Erythrocytes - drug effects; Erythrocytes - metabolism; Guinea Pigs; Inosine - blood; Kinetics; Mathematics; Methylation; Models, Biological; Octanols; Osmolar Concentration
• ISSN: 0026-895X; 1521-0111

The uptake of adenosine into erythrocytes takes place by two different mechanisms. One is saturable by high substrate concentrations, is inhibited by dipyridamole, and can be described in terms Of Michaelis-Menten kinetics. The other mechanism is proportional to the adenosine concentration and has the characteristics of diffusion across lipophilic areas of the membrane. The total uptake ( Y ) fits a model described by the equation See PDF for Equation (1) where the apparent K m and V max values are derived from the Michaelis-Menten equation, P d is the proportional constant of the simplified law of diffusion, and S is the substrate concentration. Evidence for the validity of the model was obtained by comparing the uptake of four purine derivatives, inosine, adenosine, N 6 -methyladenosine, and N 6 -dimethyladenosine. These four derivatives possess different octanol/water partition coefficients as a consequence of the different groups at C-6 of the purine molecule. The uptake by diffusion correlates with the partition coefficients of the four derivatives. Dipyridamole inhibits only the saturable part, which follows Michaelis-Menten kinetics. Which of the two uptake mechanisms predominates depends on substrate concentration, and is important for understanding the mechanism of action of dipyridamole.