Role of calcium in acetylcholine-induced desensitization in dog thyroid slices.
Incubation of dog thyroid slices with 1 microM acetylcholine (ACH) for 3 h followed by a second 2-h incubation without it induces a diminution of stimulation of glucose oxidation by ACH during a third incubation of 45 min. Using a calcium-free medium during all incubations prevents the desensitization and reduces, but does not abolish, ACH stimulation of glucose oxidation. EGTA [ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid] (2 mM) added to the calcium-free medium in all incubations prevents both refractoriness and stimulation of glucose oxidation induced by ACH. Calcium depletion during the first incubation only, achieved by using EGTA and a calcium-free medium, also prevents refractoriness but not the augmentation of glucose oxidation caused by ACH. Incubation of thyroid slices with 1 microM ionophore A23817 during the 3-h first incubation decreases the stimulation of glucose oxidation induced by its readdition or by 1 microM ACH added for the first time in the third incubation. Ionophore-induced desensitization is not related to a cholinergic muscarinic receptor effect. Initial incubation of dog thyroid slices with 1 microM ACH diminishes the subsequent stimulation of glucose oxidation by 0.5 microM ionophore. However, the ACH-induced desensitization to ionophore can be overcome by a 10-fold increase in the amount of ionophore in the third incubation. Ionophore (1 microM) in the first incubation also induces refractoriness to thyroid-stimulating hormone (TSH) (10 mU/ml)-stimulated glucose oxidation in the third incubation. In contrast, initial incubation of thyroid slices with TSH (25 mU/ml) does not affect the stimulation of glucose oxidation by 0.5 microM ionophore added during the third incubation. These results suggest that increased intracellular calcium plays a major role in, or even mediates, ACH-induced desensitization in the thyroid gland.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology; D014331:Tropicamide / Q000494:pharmacology
D000001:Calcimycin; D013972:Thyrotropin; D005947:Glucose; D014331:Tropicamide; D000109:Acetylcholine; D002118:Calcium