EFFECT OF THYROID STATUS ON β‐ADRENORECEPTORS AND MUSCARINIC RECEPTORS IN THE RAT LUNG

The effects of thyroid status on the specific binding of the muscarinic ligand (–)‐[ 3 H] quinuclidinyl benzilate (QNB) and of the β‐adrenoreceptor ligand (–)‐[ 3 H] dihydroalprenolol (DHA) in the adult rat lung were investigated. The specific binding of (–)‐[ 3 H] quinuclidinyl benzilate (QNB) to lung membranes was saturable and the equilibrium dissociation constant (K D ) determined from Scatchard analysis was 54 pM. Kinetic analysis of the binding of [ 3 H] QNB yielded a K D of 42 pM. [ 3 H] QNB binding was inhibited by muscarinic agonists and antagonists, the order of their potency was l ‐hyoscyamine>atropine>scopolamine>oxotremorine>carbachol. These data were consistent with [ 3 H] QNB binding to the muscarinic receptor. Adult male rats treated for 2 weeks with the antithyroid agent 3‐amino‐1,2,4‐triazole (ATZ) showed a 52% and 80% reduction in the serum concentration of triiodothyronine (T 3 ) and thyroxine (T 4 ) respectively. These hypothyroid rats also had a 39% decrease in the concentration of lung β‐adrenoreceptors and a 37% decrease in the concentration of lung muscarinic receptors as compared to euthyroid controls. Concurrent treatment of rats with ATZ and T 4 for 2 weeks resulted in a reduction of 15% and 20% in the concentration of lung β‐adrenoreceptors and muscarinic receptors respectively. The K D values for [ 3 H] DHA and [ 3 H] QNB binding did not change with the ATZ or ATZ + T 4 treated groups. Administration of T 4 (500 μg/kg/day) to male rats for 12 days did not result in any significant change in the concentration of either β‐adrenoreceptors or muscarinic receptors compared to euthyroid controls. No change in the K K values for [ 3 H] DHA or [ 3 H] QNB binding were detected. The results show that hypothyroid rats have a reduced lung concentration of both β‐adrenoreceptors and muscarinic receptors whereas in hyperthyroid rats these receptors do not significantly change from euthyroid controls.