Effect of thyroid status on beta-adrenoreceptors and muscarinic receptors in the rat lung.

1. The effects of thyroid status on the specific binding of the muscarinic ligand (-)-[3H]quinuclidinyl benzilate (QNB) and of the beta-adrenoreceptor ligand (-)-[3H]dihydroalprenolol (DHA) in the adult rat lung were investigated. 2. The specific binding of (-)-[3H]quinuclidinyl benzilate (QNB) to lung membranes was saturable and the equilibrium dissociation constant (KD) determined from Scatchard analysis was 54 pM. Kinetic analysis of the binding of [3H]QNB yielded a KD of 42 pM. [3H]QNB binding was inhibited by muscarinic agonists and antagonists, the order of their potency was l-hyoscyamine greater than atropine greater than scopolamine greater than oxotremorine greater than carbachol. These data were consistent with [3H]QNB binding to the muscarine receptor. 3. 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 (T3) and thyroxine (T4) respectively. These hypothyroid rats also had a 39% decrease in the concentration of lung beta-adrenoreceptors and a 37% decrease in the concentration of lung muscarinic receptors as compared to euthyroid controls. Concurrent treatment of rats with ATZ and T4 for 2 weeks resulted in a reduction of 15% and 20% in the concentration of lung beta-adrenoreceptors and muscarinic receptors respectively. The KD values for [3H]DHA and [3H]QNB binding did not change with the ATZ or ATZ+T4 treated groups. 4. Administration of T4 (500 micrograms/kg/day) to male rats for 12 days did not result in any significant change in the concentration of either beta-adrenoreceptors or muscarinic receptors compared to euthyroid controls. No change in the KD values for [3H]DHA or [3H]QNB binding were detected. 5. The results show that hypothyroid rats have a reduced lung concentration of both beta-adrenoreceptors and muscarinic receptors whereas in hyperthyroid rats these receptors do not significantly change from euthyroid controls.