Nuclei dormant

Figure 12.6 Mechanism of action of mineralocortjcoid receptor antagonists in the collecting tubule. Aldosterone enters the tubular cell by the basolateral surface and binds to a specific mineralocorticoid receptor (MNR) in the cytoplasm. The hormone receptor complex triggers the production of an aldosterone-induced protein (AlP) by the cell nucleus (NUC). The AIP acts on the sodium ion channel (ic) to augment the transport of Na+across the basolateral membrane and in to the cell. An increase in AIP activity leads to the recruitment of dormant sodium ion channels and Na pumps (P) in the cell membrane. AIP also leads to the synthesis of new channels and pumps within the cell. The increase in Na+conductance causes electrical changes in the luminal membrane that favour the excretion of intracellular cations, such as K+and H-h. Spironolactone competes with aldosterone for the binding site on the MNR and forms a complex which does not excite the production of AIP by the nucleus.

Fig. 4.3 Pouyssegur and colleagues found that in the resting dormant state of a cell (a) the MAP kinases are kept in the cytoplasm by interaction with the upstream cytosolic kinases of the MAP kinase cascade, (b) Activation of the MAP kinase cascade by a growth factor uncouples the MAPK from upstream MAPKKs and initiates translocation of MAPK to the nucleus, where it signals entry into the S phase of the cell cycle. In the nucleus, MAPK is retained by short-lived nuclear anchoring proteins. When their proteolytic removal is blocked, the residence time of MAPK in the nucleus is prolonged.

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