Desensitization of carbamylcholine-mediated cyclic GMP accumulation in dog thyroid slices

Previous studies have shown that carbamylcholine through a muscarinic receptor increases Ca2+ influx and consequently cGMP accumulation in dog thyroid slices. A first exposure to carbamylcholine induced desensitization of the cGMP response to a further exposure to this agent. The aim of this work was to investigate the role of carbamylcholine, extracellular calcium or intracellular cGMP in this desensitization. The effect of various combinations of these factors has been studied. Carbamylcholine in the absence of calcium, with and without cGMP accumulation, did not desensitize. On the other hand, an increase in intracellular calcium and its consequent cGMP accumulation did not desensitize carbamylcholine-induced cGMP accumulation either. Previous exposure of dog thyroid cells to carbamylcholine in the presence of calcium slightly decreased ionophore A23187-induced cGMP accumulation. Carbamylcholine desensitization is thus mainly homologous and bears on a step prior to cGMP synthesis. These data suggest that both carbamylcholine interaction with its receptor and extracellular calcium are necessary for desensitization. cGMP is not sufficient for this effect but its possible role is not excluded.