Mechanisms of Vesicular Uptake
Pinocytosis is the uptake of extracellular fluid with macromolecules dissolved in it by the cell. The process begins with the contact of the substance with the cell membrane, after which the membrane invaginates, forming a vacuole or vesicle. The vesicle pinches off and immerses into the cytoplasm.
The subsequent fate of the captured substrate can follow two scenarios:
- Intracellular metabolism: fusion of the vesicle with a lysosome (lysosoma) and degradation of the contents by enzymes.
- Transcytosis: the transient movement of a vesicle across the entire cell to the opposite pole, where the contents are released outward unchanged via exocytosis (exocytosis).
Receptor-Mediated Endocytosis
Unlike regular pinocytosis, this type of transport has high specificity and proceeds independently of the concentration gradient of substances.
Main stages of the process:
- Binding: the target molecule (ligand) interacts with a specific membrane receptor.
- Coat formation: the intracellular domain of the receptor binds to the protein adaptin, over which a lattice framework of the protein clathrin is assembled. A so-called coated pit is formed.
- Pinching off and uncoating: the vesicle enters the cytoplasm, sequentially sheds its clathrin coat, and then loses adaptin.
- Sorting: the free vesicle fuses with an early endosome. In the acidic environment of the endosome (at pH 5), the substance molecule detaches from the receptor. Receptors return to the cell membrane for reuse.
- Delivery: the substance is sent to organelles (e.g., to the nucleus or Golgi apparatus) or eliminated from the cell outward.
Paracellular Transport
Paracellular transport (transportus paracellularis) is the movement of substances in the aqueous phase of intercellular spaces, occurring past cells. This pathway is characteristic primarily of hydrophilic drugs and does not require energy expenditure.
Types of passive movement:
- Passive diffusion: movement of molecules along a concentration gradient (from higher to lower concentration).
- Filtration: movement driven by a pressure difference (osmotic or hydrostatic).
The main limiting factor of this pathway is the size of the transported molecules. Their diameter must not exceed the lumen of the intercellular clefts.
Anatomical Barriers for Hydrophilic Substances
The absorption of hydrophilic drugs directly depends on the histological structure of the tissue at the site of administration. For example, intestinal epithelial cells are interconnected by tight junctions (zonulae occludentes). This makes the intercellular spaces very narrow, significantly hindering the penetration of hydrophilic drugs from the intestinal lumen into the systemic circulation.
Similar obstacles to filtration are created by the renal tubular epithelium, the respiratory ciliary epithelium, and the mucous membranes of other parts of the digestive tract. As a result, hydrophilic substances are absorbed and distributed in the body extremely unevenly.