title: Sulfoconjugated catecholamines: lack of beta-adrenoceptor binding and adenylate cyclase stimulation in human mononuclear leukocytes.
abstract: 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 beta-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 beta-adrenoceptor-competing agents with lower beta-receptor affinities than the corresponding free catecholamines. No beta-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 beta-receptor ligands and must thus be regarded as a mechanism to control adrenergic action 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 beta-receptor antagonists has to be further clarified.
authors.affiliation: Department of Pathophysiology and Sport Medicine, University of Heidelberg, F.R.G.
authors.forename: G L
authors.initials: GL
authors.lastname: Michel
authors.forename: T
authors.initials: T
authors.lastname: Lenz
authors.forename: U
authors.initials: U
authors.lastname: Lernhardt
authors.forename: H
authors.initials: H
authors.lastname: Weicker
authors.forename: W P
authors.initials: WP
authors.lastname: Bieger
authors.forename: E
authors.initials: E
authors.lastname: Werle
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D002395:Catecholamines / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D020120:Iodocyanopindolol; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010869:Pindolol / Q000031:analogs & derivatives; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006719:Homovanillic Acid