Drug distribution in the Body III

Transcytosis (vesicular transport).
When new vesicles are pinched off,
substances dissolved in the extracellular
fluid are engulfed, and then ferried
through the cytoplasm, vesicles (phagosomes)
undergo fusion with lysosomes
to form phagolysosomes, and the transported
substance is metabolized. Alternatively,
the vesicle may fuse with the
opposite cell membrane (cytopempsis).
Receptor-mediated endocytosis
. The drug first binds to membrane
surface receptors whose cytosolic
domains contact special proteins (adaptins,
). Drug-receptor complexes migrate
laterally in the membrane and aggregate
with other complexes by a
clathrin-dependent process. The affected
membrane region invaginates
and eventually pinches off to form a detached
vesicle . The clathrin coat is
shed immediately , followed by the
adaptins . The remaining vesicle then
fuses with an “early” endosome,
whereupon proton concentration rises
inside the vesicle. The drug-receptor
complex dissociates and the receptor
returns into the cell membrane. The
“early” endosome delivers its contents
to predetermined destinations, e.g., the
Golgi complex, the cell nucleus, lysosomes,
or the opposite cell membrane
(transcytosis). Unlike simple endocytosis,
receptor-mediated endocytosis is
contingent on affinity for specific receptors
and operates independently of concentration
gradients.