Inotropic effects of dopamine-3-O-sulfate and dopamine-4-O-sulfate

We previously reported that dopamine (DA)-4-O-sulfate has a positive inotropic effect on isolated rabbit papillary muscle. The present study was undertaken to elucidate whether DA-3-O-sulfate has a positive inotropic effect. An attempt was also made to determine the affinity with the receptor related to the positive inotropism. DA-4-O-sulfate increased the contractile force of rabbit papillary muscle in a dose dependent manner, but synthesized DA-3-O-sulfate did not exert any significant effect. Therefore, free DA is not responsible for the positive inotropism induced by DA-4-O-sulfate. This positive inotropic effect of DA-CO-sulfate was not inhibited by beta-adrenergic, alpha-adrenergic or dopaminergic receptor antagonists. Radioligand binding assay demonstrated that both DA-4-O- and 3-O-sulfates lacked any appreciable affinity with alpha(1), alpha(2), beta(1), beta(2) or D-2 receptors. In the beating isolated heart preparation, cAMP content significantly increased after administration of DA-4-O-sulfate. Further study is needed to elucidate which receptor or channel is involved in this positive inotropism. It is demonstrated that DA-4-O-sulfate induces positive inotropic action with an increase in myocardial cAMP.