Altered thyroid status regulates the adipocyte A 1 adenosine receptor-adenylate cyclase system

Abstract

To assess the effect of hyperthyroidism on the adenosine receptor-adenylate cyclase system in adipocytes, membranes from hyperthyroid and control rats were prepared. Rats were rendered hyperthyroid by five days of injection with triiodothyronine (T 3). Basal as well as isoproterenol-sodium fluoride-, forskolin- and manganese (Mn++)-stimulated adenylate cyclase activities are attenuated 20–30% in adipocyte membranes from hyperthyroid animals. There is a greater inhibition of total adenylate cyclase activity in response to R -PIA, A 1 selective inhibitory agonist, in membranes from hyperthyroid animals. However, on a percentage basis, R -PIA is equally effective at inhibiting adenylate cyclase activity in control and treated membranes. Using antagonist radioligands, [ 3H]XAC (A 1 receptor) and [ 125I]CYP (β-adrenergic receptor), no significant alteration in receptor number is observed in hyperthyroidism. In addition, no alteration in G i protein-A 1 receptor coupling is noted as exhibited by R -PIA competition curves. These findings suggest hyperthyroidism most likely results in a decrease of the catalytic moiety of adenylate cyclase either quantitatively or functionally.