RITODRINE INHIBITION OF THE PLASMA-MEMBRANE CA2-ATPASE FROM HUMAN ERYTHROCYTE()

The Ca2+-ATPase activity of human erythrocyte membrane can be inhibite d in vitro by ritodrine, a beta(2)-adrenergic agonist. The inhibitory profile shows a low-affinity interaction and no competition with the s pecific transport and catalytic substrates. The activated conformation of the enzyme tin the presence of calmodulin or after trypsin digesti on) facilitates the interaction with ritodrine. This suggests that the C-terminal tail of the enzyme plays a protective role. By studying se lected partial reactions of the catalytic and transport cycle we found that the inhibition can be basically assigned to a lower rate of phos phorylation by ATP. A minor effect on the phosphorylation level by P-i in the absence of Ca2+ and no effect on the enzyme affinity for Ca2or ATP were also observed. The inhibition of the plasma membrane Ca2+- ATPase by ritodrine shows a clear similarity with that of the sarcopla smic/endoplasmic reticulum membrane. The inhibition under study does n ot foresee a pharmacological effect of ritodrine on the myometrial pla sma membrane Ca2+-ATPase when administered for the management of prete rm labor. (C) 1998 Academic Press.