Ritodrine inhibition of the plasma membrane Ca2+-ATPase from human erythrocyte.

The Ca(2+)-ATPase activity of human erythrocyte membrane can be inhibited in vitro by ritodrine, a beta 2-adrenergic agonist. The inhibitory profile shows a low-affinity interaction and no competition with the specific transport and catalytic substrates. The activated conformation of the enzyme (in the presence of calmodulin or after trypsin digestion) facilitates the interaction with ritodrine. This suggests that the C-terminal tail of the enzyme plays a protective role. By studying selected partial reactions of the catalytic and transport cycle we found that the inhibition can be basically assigned to a lower rate of phosphorylation by ATP. A minor effect on the phosphorylation level by Pi in the absence of Ca2+ and no effect on the enzyme affinity for Ca2+ or ATP were also observed. The inhibition of the plasma membrane Ca(2+)-ATPase by ritodrine shows a clear similarity with that of the sarcoplasmic/endoplasmic reticulum membrane. The inhibition under study does not foresee a pharmacological effect of ritodrine on the myometrial plasma membrane Ca(2+)-ATPase when administered for the management of preterm labor.