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The β-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in β-adrenergic receptor kinase (βARK) expression. βARK is thought to effect desensitization by acting in concert with an inhibitor protein, called β-arrestin. Two isoforms have been identified both for βARK and for β-arrestin. In the present study, we have investigated the expression of the individual isoforms of β-arrestin and of βARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, β-arrestin-1, β-arrestin-2, βARK-1, and βARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for β-arrestin-1 and β-arrestin-2, a slight (<50%) increase of the mRNA for βARK-2, and a threefold increase for βARK-1 mRNA. At the protein level, β-arrestin-1 was readily detected by Western blotting in human heart. Its absolute values were ≈350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. β-Arrestin-2 levels were too low to be detectable using the same methods. βARK levels as determined by enzymatic activity were ≈20 fmol/mg cytosolic protein (βARK-1 plus βARK-2) and thus almost 20-fold lower than those of β-arrestin. βARK levels were increased approximately twofold in heart failure. We hypothesize that, because of its low expression, βARK may be the limiting component in β-adrenergic receptor desensitization in the human heart and that upregulation of βARK-1 expression in heart failure may, therefore, play a major role in the desensitization of these receptors.