Elevation of Cyclic Guanosine 3′,5′-Monophosphate Levels in Dog Thyroid Slices Caused by Acetylcholine and Sodium Fluoride

Abstract

Abstract Cyclic guanosine 3',5'-monophosphate (cyclic GMP) levels were determined in dog thyroid slices using the protein-binding method. [3H]Guanine incorporation into cyclic GMP was also determined by thin layer chromatography. Basal levels of cyclic GMP in dog thyroid slices were usually 10 to 30 pmoles per g wet tissue. These values were at least 10-fold lower than the cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels. Cyclic GMP levels were significantly increased by acetylcholine (5.5 x 10-7 m to 5.5 x 10-5 m) and NaF (10-2 m) after a 1-min incubation. Increases (5 to 10-fold) were observed after 5- and 20-min incubations with acetylcholine (5.5 x 10-5 m) and after a 20-min incubation with NaF (10-2 m). Neither thyroid-stimulating hormone (100 milliunits per ml) nor prostaglandin E1 (2.8 x 10-5 m) increased cyclic GMP levels during 1-,5-, and 20-min incubations. Acetylcholine and NaF also increased [3H]guanine incorporation into cyclic GMP. The effect of acetylcholine was inhibited by atropine (1.6 x 10-4 m). Acetylcholine and NaF had little or no effect on cyclic AMP levels, while thyroid-stimulating hormone and prostaglandin E1 markedly increased cyclic AMP concentrations. In liver slices of the rat, acetylcholine increased cyclic GMP levels 2-fold, but NaF had no effect. These results indicate that the levels of cyclic GMP and cyclic AMP in dog thyroid slices are regulated by separate hormonal and metabolic mechanisms.