Studies on Secretion of Catecholamines Evoked By DMPP and McN-A-343 in the Rat Adrenal Gland

흰쥐 적출 부신에서 DMPP 및 McN-A-343의 Catecholamine 분비작용에 관한 연구

The characteristics and differences between DMPP and McN-A-343 on the secretory effect of catecholamines(CA) were studied in the isolated perfused rat adrenal glands. DMPP(100 uM) and McN-A-343(100 uM) perfused into an adrenal vein of the gland casued significant increases in CA secretion. On molar basis the secretory effect of McN-A-343 was about one fifth as potent as that of DMPP. Tachyphylaxis to releasing effects of CA evoked by DMPP and McN-A-343 was not observed by repeated perfusion of these agents. The DMPP-evoked CA secretion was significantly inhibited by pretreatment with chlorisondamine, desipramine and profusion of $Ca^{2+}-free$ Krebs solution containing EGTA, while it was not affected by pirenzepine, ouabain and physostigmine. However, pretreatment with atropine rather enhanced CA release by DMPP. The releasing effect of CA induced by McN-A-343 was markedly depressed by pretreatment with atropine, pirenzepine, chlorisondamine, physostigmine, and perfusion of $Ca^{2+}-free$ medium plus EGTA but was not influenced by desipramine, except for the case of ouabain which clearly potentiated CA release by McN-A-343. These experimental results suggest that both DMPP and McN-A-343 cause greatly secretion of CA from the isolated perfused rat adrenal glands by a calcium-dependent exocytotic mechanism. The secretory effect of DMPP is due to the stimulation of cholinergic nicotinic receptors and the secretion by McN-A-343 via activation of selecive $M_{1}-muscarinic$ receptors in the adrenal gland. It is also thought that the DMPP-evoked secretory effect is much greater than McN-A-343-induced effect.

흰쥐 적출 부신에서 DMPP와 McN-A-343의 카테콜아민(CA) 분비작용의 차이와 특성에 대해서 연구한 결과 다음과 같다. DMPP(100 uM)와 McN-A-343(100 uM)은 부신정맥내로 투여시 유의한 카테콜아민 분비작용을 나타내었다. Mol농도로 비교시 McN-A-343의 CA분비작용은 DMPP의 약 1/5정도였다. DMPP나 McN-A-343의 반복투여시 반응 급강현상은 관찰할 수 없었다. DMPP의 CA분비작용은 chlorisondamine이나 desipramine또는 $Ca^{2+}-free$ Krebs + EGTA 관류등의 전처치로 의의있게 억제되었으나, pirenzepine, ouabain 및 physostigmine등 전처치에 의해서는 영향을 받지 않았다. 그러나 atropine 전처치시 DMPP의 분비작용은 오히려 증강되었다. McN-A-343의 CA분비작용은 atropine, pirenzepine, chloriondamine, physostigmine 및 $Ca^{2+}-free$ medium plus EGTA 관류등의 전처치에 의해서현처히 차단되었으나 desipramine등에 의해서는 영향을 받지 않았다. 그러나 ouabain의 전치치시 McN-A-343의 분비효과는 크게 증강되었다. 이상의 실험결과로 보아 DMPP와 McN-A-343은 횐쥐 적출관류 부신에서 현저한 CA분비작용을 일으키며, 이는 $Ca^{2+}$ 의존성 임을 보였으며, DMPP의 분비작용은 부신의 nicotine 수용체의 흥분을 통해서 나타내며, 또한 McN-A-343의 분비작용은 $M_{1}-muscarine$ 수용체의 흥분에 의하여 유발되는 것을 생각된다. DMPP의 분비활성이 McN-A-343보다 훨씬 강력한 것으로 사료된다.