The Role of Calcium and Guanosine 3′: 5′‐Monophosphate in the Action of Acetylcholine on Thyroid Metabolism

Abstract

The role of Ca and cyclic[c]GMP in the regulation of thyroid metabolism was investigated in dog thyroid slices. Carbamoylcholine enchanced glucose carbon-1 oxidation, protein iodination, cGMP accumulation and decreased thyrotropin-induced cAMP accumulation and I secretion; it did not affect protein synthesis. The effects of carbamoylcholine were reproduced under various experimental conditions by supplementary Ca in the medium, ouabain and in media in which Na+ was replaced by choline chloride. They were inhibited by La. Free intracellular Ca2+ apparently is the intracellular signal for carbamoylcholine effects. A Na+-gradient-driven Ca2+ extrusion mechanism apparently operates in the thyroid cell. Mn2+ reproduced the effect of Ca2+ on glucose oxidation, protein iodination and cGMP accumulation in Ca2+-depleted slices and medium, and thus mimicked some intracellular effects of Ca2+. Mn2+ inhibited the carbamoylcholine effect on thyrotropin-induced thyroid secretion and cAMP accumulation, and Ca2+ inhibited the Mn2+-induced cGMP accumulation. The 2 ions apparently compete for the same channel. Similarly Mn2+ inhibited Ca effects in the presence of ionophore A23187 [2-[(3.beta.-9.alpha.,11.beta.-trimethyl)-8-(2-pyrrole carboxy methyl)-1,7-dioxaspiro[6.6]undecyl-2.beta.-methyl]-5-methylaminobenzoxazole-4-carboxylic acid]. Procaine inhibited protein iodination under all conditions suggesting a primary effect; it also inhibited all carbamoylcholine and ouabain actions. The drug did not inhibit the effects of choline chloride and its action was reversed by raising carbamoylcholine but not Ca2+ concentration; it is doubtful that procaine acts by blocking Ca2+ channels. In media without added Ca2+, Mn2+ increased cGMP accumulation but did not decrease thyrotropin-induced cAMP accumulation or I secretion, which suggests that cGMP cannot be the sole mediator of the latter 2 effects of carbamoylcholine.