title: Inhibition of tyrosine hydroxylase in rabbit mesenteric artery and vas deferens by catechol oestrogens.
abstract: In the present study we have investigated the effects of oestrogens, catechol oestrogens, and catecholamines on tyrosine hydroxylase (TH) activity derived from rabbit mesenteric artery and vas deferens. Both catechol oestrogens, 2-hydroxyoestradiol (2OHE2) and 2-hydroxyoesterone (2OHE1), inhibited TH activity in mesenteric artery and vas deferens in a concentration-dependent manner with potencies that were higher than those for noradrenaline but lower than that for dopamine. When added to the reaction medium along with increasing concentrations of a pterin cofactor (200 to 1,500 mumol/l DMPH4), the catechol oestrogens (200 mumol/l) increased the apparent Km for DMPH4 without altering the maximum velocity (Vmax) of the reaction. Similar results were obtained with the addition of noradrenaline (200 mumol/l) and dopamine (120 mu/mol). Apparent Ki values obtained for the catecholamines and catechol oestrogens were within the same order of magnitude and varied from 30 mumol/l for dopamine and 2OHE2 to 183 mumol/l for 2OHE1. Oestradiol (E2) and 2-methoxyoestradiol (2MeOE2), i.e., oestrogens that do not possess a catechol moiety, exhibited only weak inhibitory effects on TH activity. At the highest concentration tested (1 mmol/l), they did not reduce enzyme activity below 58% of control values. Kinetic analysis revealed that these two oestrogens did not consistently affect either the Vmax of hydroxylation or the Km for DMPH4. It is concluded that catechol oestrogens inhibit TH activity with a potency comparable to noradrenaline and dopamine. This inhibition is by competition with the pterin cofactor. Oestrogens that to not possess a catechol moiety are not effective inhibitors of TH.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002393:Estrogens, Catechol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009647:Normetanephrine / Q000494:pharmacology; D011817:Rabbits; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D014649:Vas Deferens / Q000187:drug effects / Q000201:enzymology
chemical_list: D002395:Catecholamines; D002393:Estrogens, Catechol; D009647:Normetanephrine; D014446:Tyrosine 3-Monooxygenase