Tetrahydropapaveroline inhibits dopamine uptake in rat brain synaptosomes.
THP, which can be formed by the condensation of dopamine with dopaldehyde, has been proposed to be involved in mediating some of the effects of ethanol on the central nervous system. We have observed that THP induces small granular vesicles (SGVs), visible with the electron microscope, in central dopamine fibers (Koda et al., 1978). In order to investigate the mechanism of SGV induction by THP, we examined dopamine and THP uptake into synaptosomes. [3H]THP (1.25 Ci/mmole), prepared by catalytic exchange labeling, exhibited no active uptake into synaptosomes (kinetics consistent with simple diffusion). THP did exhibit competitive inhibition (Ki = 4.2 x 10(-5) M) of [3H] dopamine uptake (Km = 2.6 x 10(-7) M; Vmax = 8.5 nmoles/min/g pellet) in these preparations. It is unlikely that endogenous THP would accumulate to concentrations sufficiently high to inhibit dopamine uptake under physiological conditions.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003342:Corpus Striatum / Q000378:metabolism; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D010208:Papaverine / Q000031:analogs & derivatives*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D013765:Tetrahydropapaveroline / Q000494:pharmacology*
D013765:Tetrahydropapaveroline; D010208:Papaverine; D004298:Dopamine