DESENSITIZATION OF CARBAMYLCHOLINE-MEDIATED CYCLIC-GMP ACCUMULATION IN DOG THYROID SLICES

Carbamylcholine through a muscarinic receptor increases Ca2+ influx and consequently cGMP accumulation in dog thyroid slices. A 1st exposure to carbamylcholine induced desensitization of the cGMP response to a further exposure to this agent. The role of carbamylcholine, extracellular Ca or intracellular cGMP in this desensitization. The effect of various combinations of these factors has been studied. Carbamylcholine in the absence of Ca, with and without cGMP accumulation, did not desensitize. An increase in intracellular Ca 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. Evidently, both carbamylcholine interaction with its receptor and extracellular Ca are necessary for desensitization. cGMP is not sufficient for this effect but its possible role is not excluded.