항우울제의 타액분비 감소효과에 대한 세포내 칼슘증가제의 영향

Agents increasing intracellular calcium levels ameliorate the antodepressant-induced reduction of submandibular salivation in cast

Tri- and tetra-cyclic antidepressants are known to cause dry mouth among other several major complications. The present study was designed to compare the degree of reduced salivation due to antidepressants and to explore whether intracellular calcium-increasing agents ameliorate the salivation. Effects of antidepressants and agents increasing intracellular calcium on the cholinergic submandibular secretion and blood flow induced by the chorda stimulation or intra-arterial acetylcholine were observed in anesthetized cats. Effects of antidepressants and calcium-mobilizing agents on K+ efflux were also observed in excised gland slices. The results obtained were as follows: 1. Salivary secretion in response to the chorda stimulation (3 V, 20 Hz, 1 msec) was significantly attenuated by antidepressants in a dose-dependent manner, whereas the blood flow was not affected. 2. Salivary secretion and increased blood flow evoked by intra-arterial acetylcholine (20 μg/kg) were markedly diminished by antidepressants, the magnitude of which was amitryptyline>imipramine > mianserin in order. 3. Cholinergic salivation was significantly decrease by cyclopiazonic acid, a calcium pump inhibitor of the endoplasmic reticulum, or by BAPTA/AM, a specific intracellular calcium chelator. 4. Caffeine and ryanodine potentiated the cholinergic salivation and ameliorated the depressed salivary secreation due to antidepressants. 5. Calcium ionophore A 23187 ameliorated the depressed salivation due to antidepressants. 6. Antidepressants inhibited the K+ efflux, which were restored by caffeine or A 23187. These results suggest that the depressed salivary secreation due to antidepressants is ameliorated by increasing intracellular calcium levels.