Thyroid hormone inhibits purified taste bud membrane adenosine 3',5'-monophosphate phosphodiesterase activity.
Thyroid hormone inhibited purified taste bud membrane adenosine 3'5'-monophosphate (cAMP) phosphodiesterase (PDE) activity in a dose-dependent manner. Taste bud membrane cAMP PDE was inhibited most effectively by thyroxine (T4) followed in order by triiodothyionine (T3), diiodotyrosine (DIT) and monoiodotyrosine (MIT). Concentrations required for 50% inhibition (IC50) of enzyme activity were about 1 x 10(-6), 1 x 10(-5), 6 x 10(-4) M and greater than 1 x 10(-3) M for T4, T3, DIT and MIT, respectively. Addition of zinc at physiological concentrations found in serum greatly augmented the inhibitory effects of T4 and T3 at lower concentrations (10(-7) and 10(-6) M, respectively) resulting in further inhibition of cAMP PDE by 40-50%. Inhibition of cAMP PDE by T4 appears to be relatively tissue selective as indicated by the IC50 of 1 x 10(-6) M for the taste bud but only 7 x 10(-6) M, 3 x 10(-5) M, and 4 x 10(-5) M, for heart, kidney and brain cAMP PDE, respectively. Inhibition of taste bud membrane cAMP PDE by T4 was competitive with substrate cAMP with a Ki of 4 microM. These results suggest that inhibition of cAMP PDE, which increases taste bud membrane intracellular cAMP, may participate in the action of thyroid hormone in the taste process.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008566:Membranes / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013650:Taste Buds / Q000201:enzymology*; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D013963:Thyroid Hormones; D014284:Triiodothyronine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015032:Zinc; D013974:Thyroxine