Delta-9-tetrahydrocannabinol and theophylline: in vitro interaction with bovine serum albumin.

ABSTRACT

Delta-9-tetrahydrocannabinol (delta-9-THC) (1.6 x 10(-6) M-13.33 x 10(-6) M) and theophylline (11.0 x 10(-6) M-550.0 x 10(-6) M) both bind to bovine serum albumin (BSA) and the binding is linear with respect to concentration. Further, it is observed that delta-9-THC both at low (1.6 x 10(-6) M and 6.4 x 10(-6) M) and high (13.33 x 10(-6) M) concentrations inhibits the binding of theophylline to BSA; whereas theophylline (11.0 x 10(-6) M-550.0 x 10(-6) M) promotes the binding of delta-9-THC to BSA. Kinetic analysis (using Scatchard plots) shows that delta-9-THC (1.6-13.33 x 10(-6) M) reduces the high affinity binding constant (K1) and the number of low affinity binding sites (n2) of theophylline to BSA; while its low affinity binding constant (K2) increased without affecting the number of high affinity binding sites (n1) under identical conditions. Further, it is observed that at lower concentrations (1.6-6.4 x 10(-6) M) delta-9-THC exerts greater effect on the binding parameters of theophylline-BSA interactions as compared to the effect observed with its high concentration (13.33 x 10(-6) M). Theophylline (11.0-550.0 x 10(-6) M). on the other hand, increases the affinity of the binding of delta-9-THC to BSA without changing the number of its binding sites. These suggest that (a) delta-9-THC and theophylline bind at different sites of BSA molecules and (b) the two drugs interfere with each other in their individual binding with the molecular orientation of the BSA molecule.