Altered thyroid status regulates the adipocyte A1 adenosine receptor-adenylate cyclase system.
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 (T3). 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, A1 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 (A1 receptor) and [125I]CYP (beta-adrenergic receptor), no significant alteration in receptor number is observed in hyperthyroidism. In addition, no alteration in Gi protein-A1 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.
Bumgarner
J R
JR
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Ramkumar
V
V
Stiles
G L
GL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D002462:Cell Membrane; D005576:Colforsin / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000378:metabolism*; D014284:Triiodothyronine
D011983:Receptors, Purinergic; D014284:Triiodothyronine; D005576:Colforsin; D008345:Manganese; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D005459:Fluorides