Dopamine拮抗剤およびdopamineの電解質ステロイド分泌におよぼす影響
スポンサーリンク
概要
- 論文の詳細を見る
There is considerable information suggesting that dopamine is a physiological regulator of aldosterone secretion. Metoclopramide, a specific dopamine antagonist, elicits a rapid rise in plasma aldosterone independent of the known aldosterone-regulating factors. However, the mechanism and the site of action of metoclopramide, whether adrenal or extraadrenal, in stimulation of aldosterone production remain to be defined. The present studies were designed to investigate the mechanism of dopaminergic control of corticosteroid secretion and to determine at which step in the aldosterone biosynthetic pathway metoclopramide and dopamine exert their effect.<BR>Plasma concentrations of progesterone, 11-deoxycorticosterone (DOC), and cortisol were not altered by a bolous intravenous administration of 10 mg metoclopramide in 8 healthy male volunteers. Metoclopramide increased plasma aldosterone from 6.9±2.8 (Mean±2SD) ng/100 ml to a maximum level of 18.2±4.7 ng/100 ml, 18-hydroxycorticosterone 0.09μg/100 ml to a maximum of 0.85±0.22 μg/100 ml. The aldosterone, 18-OHB and corticosterone responses displayed a parallel time course, with a significant response of each occurring within 5 minutes after metoclopramide administration. These data suggest that metoclopramide may modulate the activities of 18-hydroxylase and 1113-hydroxylase.<BR>Studies in vitro revealed that metoclopramide (10<SUP>-8</SUP>-10<SUP>-4</SUP>M) had little effect on basal production of aldosterone, 18-OHB and corticosterone from human adrenal slices. Dopamine (10<SUP>-4</SUP>M) did not alter the basal secretion of aldosterone, 18-OHB and corticosterone, but suppressed the secretion of these 3 mineralocorticoids by ACTH, which were diminished by addition of 10<SUP>-4</SUP> M metoclopramide.<BR>There was a concentration-dependent inhibitory effect of dopamine on conversion of corticosterone to 18-OHB and DOC to corticosterone in vitro using bovine adrenal mitochondrial fractions. IC<SUB>50</SUB> of dopamine inhibiting 18-hydroxylation and 11β-hydroxylation were 7.5×10<SUB>-7</SUB>M and 9.5×10<SUB>-4</SUB>M, respectively. It appears that physiological concentration of dopamine can modulate the activity of 18-hydroxylase enzyme.<BR>In summary, it can be concluded that the <I>in vivo</I> and <I>in vitro</I> studies are compatible with a view that dopamine has a physiological role in the regulation of aldosterone by modulating the activity of 18-hydroxylase enzyme.
- 一般社団法人 日本内分泌学会の論文
著者
-
福地 総逸
福島県立医科大学
-
伊藤 信雄
福島県立医科大学第三内科
-
柳沼 健之
福島県立医科大学第三内科
-
柳沼 健之
福島県立医科大学 内科学第3講座
-
伊藤 信雄
福島県立医科大学第3内科
-
小島 元子
福島県立医科大学第3内科
-
草野 良郎
福島県立医科大学第3内科
-
斎藤 万一郎
福島県立医科大学第三内科
関連論文
- 副腎偶発腫瘍からみた内科学の進歩
- 経皮的穿刺生検による副腎腫瘍の術前組織診断法 (自信を持って勧められる我が科の最新医療技術)
- 腎炎、腎不全(Primary careにおける種々疾患の診断と治療のポイント)
- 代謝・内分泌疾患(Primary careにおける種々疾患の診断と治療のポイント)
- 心膜切除術により心機能が著明に改善した結核性収縮性心膜炎の1例 : 日本循環器学会第100回東北地方会
- 16)Regitine投与後著明な血圧上昇を認めβ-受容体機能亢進状態を呈した低レニン性本態性高血圧症の1例 : 日本循環器学会第76回東北地方会
- 本態性高血圧症のレニン分泌に対する交感神経β受容体の役割
- 11β-hydroxylase 障害
- デキサメサゾン長期投与による原発性アルドステロン分泌過剰症の鑑別診断
- 本態性高血圧症のインスリン抵抗性の成因における交感神経β_2受容体の意義