Physiological significance of plasma sulfoconjugated dopamine: experimental and clinical studies.
Sulfoconjugated catecholamines have been regarded simply as metabolites of free catecholamines. However, a conjugated form of the catecholamine, dopamine has recently attracted much attention because it is present at high levels in the plasma of humans and experimental animals. We carried out experimental and clinical studies to determine the physiological significance of this large amount of dopamine conjugate in the plasma. Clinical studies showed that the plasma level of dopamine sulfate decreased significantly during the acute phase of heart failure, whereas that of free dopamine increased. Moreover, the plasma level of conjugated dopamine in patients with essential hypertension was higher than that in control subjects, and being highest in patients with renal hypertension. In experimental studies, we examined the activity for deconjugating DA sulfate in homogenates of organs from dogs. The kidney and liver exhibited the highest activities, and in the heart, the activity was higher in the atrium than the ventricle. We also examined the effect of dopamine sulfate on isolated perfused rat heart. Dopamine sulfate was found to be converted to free dopamine, which was responsible for the positive inotropic action, in atrial tissue. Moreover, deconjugation of DA sulfate to the free form was accelerated by a high work lord on the heart. From these results, we conclude that the formation of dopamine sulfate plays a role in regulating the level of plasma free dopamine and that plasma dopamine sulfate may be a storage or reserve form of dopamine. Free (or active) dopamine may be formed through a deconjugation reaction when necessary.
Department of Pharmacology, School of Medicine, University of Tokushima, Japan.
M
M
Yoshizumi
Y
Y
Ishimura
Y
Y
Masuda
T
T
Ohuchi
I
I
Katoh
H
H
Houchi
M
M
Oka
D000328:Adult; D000818:Animals; D015239:Arylsulfotransferase / Q000097:blood; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004298:Dopamine / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011921:Rats, Inbred WKY; D013431:Sulfates / Q000097:blood*
D002395:Catecholamines; D013431:Sulfates; D015239:Arylsulfotransferase; D004298:Dopamine