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.