Sulfoconjugated catecholamines: lack of β-adrenoceptor binding and adenylate cyclase stimulation in human mononuclear leukocytes

The racemic 3-O-sulfates of epinephrine and norepinephrine as well as 4-O-sulfoconjugated dopamine were synthesized, highly purified and investigated with respect to their β-adrenoceptor affinities and relative potencies in the receptor-coupled adenylate cyclase system in isolated human mononuclear leukocytes. The receptor affinities of all catecholamine sulfates were reduced at least 1 000-fold when compared to those of the free catecholamines. Furthermore, catecholamine sulfoconjugates did not produce intracellular cAMP signals. In contrast to the sulfated catecholamine metabolites, the 3-O-methylated catecholamines metanephrine and normetanephrine were found to behave as endogenous β-adrenoceptor-competing agents with lower β-receptor affinities than the corresponding free catecholamines. No β-receptor agonist activity in the adenylate cyclase system was found with metanephrine and normetanephrine. Our data provide direct evidence that sulfoconjugation renders catecholamines inactive as β-receptor ligands and must thus be regarded as a mechanism to control adrenergic actin at the prereceptor level by a buffering of the concentration of free catecholamines. The physiological significance of a potential role of 3-O-methylated catecholamines as endogenous β-receptor antagonists has to be further clarified.