Physiological Pharmaceutics

Membranes and barriers 9Figure 1.6 Intestinal epithelium illustrating the various types of junctionbloodstream. In epithelial tissues there is a need for a more effective chemical and physicalbarrier, and as a result the epithelial cells are bonded together by a number of different typesof junctions which prevent diffusion of solutes around the cells. The primary types are(Figure 1.6):a) tight junctions or zonulae occludensb) gap junctionsc) desmosomes or zonulae adherens.Tight junctionsTight junctions are formed when specific proteins in two adjacent plasma membranes makedirect contact across the intercellular space (Figure 1.7). A belt-like structure composed ofmany protein strands completely encircles each cell in the epithelium, attaching it to itsneighbours and sealing the outer (luminal) space from the interior of the tissue or organ. Ata tight junction, the interacting plasma membranes are so closely apposed that there is nointercellular space and the membranes are within 2Å of each other. As these junctions canbe disrupted either by treatment with proteolytic enzymes or by agents that chelate Ca 2+ orMg 2+ , both the proteins and divalent cations are thought to be required for maintaining theirintegrity. Beneath the tight junction, the spaces between adjacent cells are wider 5 . Thestructure of the epithelium has been likened to “a six-pack of beer extended indefinitely in2 dimensions” 6 .Tight junctions play a critical part in maintaining the selective barrier function of cellsheets. For example, the epithelial cells lining the small intestine must keep most of the gutcontents in the lumen. Simultaneously, the cells must pump selected nutrients across the cell