We previously reported that dopamine (DA)-4-O-sulfate has a positive i
notropic effect on isolated rabbit papillary muscle. The present study
was undertaken to elucidate whether DA-3-O-sulfate has a positive ino
tropic effect. An attempt was also made to determine the affinity with
the receptor related to the positive inotropism. DA-4-O-sulfate incre
ased the contractile force of rabbit papillary muscle in a dose depend
ent manner, but synthesized DA-3-O-sulfate did not exert any significa
nt effect. Therefore, free DA is not responsible for the positive inot
ropism 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 demonstra
ted 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 be
ating isolated heart preparation, cAMP content significantly increased
after administration of DA-4-O-sulfate. Further study is needed to el
ucidate which receptor or channel is involved in this positive inotrop
ism. It is demonstrated that DA-4-O-sulfate induces positive inotropic
action with an increase in myocardial cAMP.