Adducin

Adducin is a cellular protein that is part of the cytoskeleton .

With actin and spectrin , it can form a two-dimensional network of pentagonal and hexagonal structures below the cell membrane . Adducin binds to the ends of the actin filaments and functions as an actin-bundling cap protein. The adducins consist of α-, β- and γ-adducin, for each of which the genes are known. In its active form, adducin occurs as a heterodimer of its α-, β-form (or α-γ). In the kidney (tubule) the adducin is involved in the binding of the α-subunit of Na ⁺ / K ⁺ -ATPase with the spectrin-actin membrane cytoskeleton. The activity of adducin depends on its degree of phosphorylation (by protein kinase C and A) and the intracellular Ca + concentration.

Adducin and high blood pressure

A polymorphism of α-adducin (Gly 460Trp mutation), which is directly related to a chronic increase in blood pressure, was found in hypertensive rats, but also in humans ( hypertension of the saline-sensitive type). Adducin appears to play an interactive role in the pathogenesis of high blood pressure, with endogenous ouabain also playing a role. It is assumed that adducin has a regulatory function for the Na ⁺ / K ⁺ -ATPase in the kidney cells and is able to influence blood pressure . The known mutation of the α-adducin leads to a stimulation of the Na ⁺ / K ⁺ -ATPase. In the renal tubule, this leads to sodium retention with a subsequent increase in blood pressure.

Therefore, adducin and ouabain are starting points for several newer drugs (e.g. rostafuroxin , a digitoxigenin derivative) for the treatment of high blood pressure. These agents are antagonists of endogenous ouabain (or the isomer of ouabain, g-strophanthin ). A known mutation of α-adducin can have therapeutic consequences in people with essential high blood pressure, because it has been shown that people with the mutated form of α-adducin respond particularly well to certain diuretics ( thiazides ).

literature

• Iwamoto, T. & Kita, S. (2006): Hypertension, Na ⁺ / Ca ²⁺ exchanger, and Na ⁺ / K ⁺ ATPase. In: Kidney Int . Vol. 69, pp. 2148-2154. PMID 16641927
• Manunta, P. et al. (2006): A new antihypertensive agent that antagonizes the prohypertensive effect of endogenous ouabain and adducin. In: Cardiovasc. Hematol. Agents. Med. Chem. Vol. 4, pp. 61-66. PMID 16529550