Kinetics of tyramine transport and permeation across chromaffin-vesicle membranes.
Tyramine permeates chromaffin-granule membranes via a reserpine-insensitive mechanism. The rate is unsaturable and increases with pH, indicating permeation of the unprotonated form of the amine. Reserpine-insensitive dopamine uptake is at least 10 times slower, consistent with dopamine's lesser lipophilicity. Dopamine is transported into chromaffin-granule membrane vesicles via a saturable, reserpine-sensitive, proton-linked mechanism. Tyramine inhibits dopamine transport with a Ki of 5-10 microM. Tyramine is not accumulated nearly as well as dopamine because inward transport is opposed by outward permeation. Nevertheless, the velocity of reserpine-sensitive tyramine transport can be deduced from the steady-state level of tyramine accumulation and the rate of permeation. Vmax for tyramine transport is about one-third of the value for dopamine transport. Therefore, two aromatic hydroxyls are not needed for monoamine transport but are required for efficient accumulation and storage.
D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002417:Cattle; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D010539:Permeability; D012110:Reserpine / Q000494:pharmacology; D014439:Tyramine / Q000378:metabolism*
D012110:Reserpine; D004298:Dopamine; D014439:Tyramine