Description:
<jats:p>Upon addition of methylamine to intact cells, this lysosomotropic weak base accumulates intracellularly as the result of at least two different mechanisms: (1) facilitated diffusion across the plasma membrane, i.e. a process which is carrier-mediated and subject to both trans-stimulation (accelerative exchange) and cis-inhibition (competition) by other amines (e.g. ammonia, methylamine and triethylamine); this transport process is furthermore non-concentrative, energy-independent, and (although moderately temperature-sensitive) operative even at 0 degrees C; (2) active uptake, i.e. an energy-dependent concentrative process which is inhibited by anoxia and energy inhibitors. With time, methylamine accumulates in lysosomes and gives rise to a lysosomal swelling which is easily visible by optical microscopy, and which causes the cells to appear coarsely granular. After a 1h incubation with 10mM-methylamine, the total cell volume is increased by about 12%. Under anoxic conditions or in the presence of energy inhibitors, lysosomal swelling is abolished regardless of there being a high concentration of methylamine intracellularly (taken up by facilitated diffusion). The continuous accumulation of methylamine in lysosomes therefore seems to depend on an energy-requiring process (such as continuous proton pumping), and not only on trapping by Donnan-equilibrium-generated protons.</jats:p>