FACILITATION OF NORADRENALINE RELEASE FROM SYMPATHETIC-NERVES THROUGH ACTIVATION OF ACTH RECEPTORS, BETA-ADRENOCEPTORS AND ANGIOTENSIN-II RECEPTORS
FACILITATION OF NORADRENALINE RELEASE FROM SYMPATHETIC-NERVES THROUGH ACTIVATION OF ACTH RECEPTORS, BETA-ADRENOCEPTORS AND ANGIOTENSIN-II RECEPTORS
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DOI：
10.1111/j.1476-5381.1988.tb11730.x
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发表时间：
1988-11-01
影响因子：
7.3
通讯作者：
MAJEWSKI, H
中科院分区：
文献类型：
--
作者：
COSTA, M;MAJEWSKI, H
在预先与去甲肾上腺素孵育的兔肺动脉和左心房条上，促肾上腺皮质激素的活性片段(ACTH124，0.1µm)在含有皮质酮(40µm)、可卡因(30µm)和心得安(4µm)的鸡尾酒存在时，可显著增强刺激(S I)引起的放射性外流，但在没有这些药物的情况下不显著。在兔的肺动脉中，ACTH1-24(0.1µm)对可卡因(30µm)也有易化作用。无论有无皮质酮(40微米)、可卡因(30微米)和心得安(4微米)的混合液存在或不存在时，ACTH_1-24(0.1U/M)均不影响大鼠心房、大鼠和豚鼠肺动脉的S-I流出。这些结果表明，易化结合ACTH受体的存在可能仅限于兔的交感神经末梢。血管紧张素II(0.01µm)显著增加兔肺动脉S-I的放射性流出量，而异丙肾上腺素(0.1µm)和ACTH_(-24)(0.1µm)则无显著作用。在酚妥拉明(1µm)阻断抑制性α2-肾上腺素能受体的情况下，血管紧张素II(0.01µm)的易化作用显著增强，异丙肾上腺素(0.1µm)和ACTH1-24(0.1µm)也有显著的易化作用。这些结果表明，反馈抑制去甲肾上腺素的释放，通过α2-肾上腺素受体机制，在激活易化的连接前受体的过程中，缓冲去甲肾上腺素的释放。在兔肺动脉，两种浓度的8-溴-环磷酸腺苷(270或540微米)对酚他拉明(1微米)引起的S-I的放射性流出均有类似的增强作用。在8-溴-环状AMP(270微米)和酚妥拉明存在下，异丙肾上腺素(0.1微米)和ACTH1-24(0.1微米)的易化作用被阻断，而血管紧张素II(0.01微米)的易化作用不变。这些结果表明，交感前β-肾上腺素受体和ACTH受体均通过产生环状AMP促进去甲肾上腺素的释放。血管紧张素II促进去甲肾上腺素释放的机制可能不依赖于环状AMP第二信使通路。
In rabbit pulmonary artery and left atrial strips previously incubated with [3H]-noradrenaline, the active fragment of adrenocorticotropic hormone (ACTH1-24, 0.1 .mu.M) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity when a cocktail containing corticosterone (40 .mu.M), cocaine (30 .mu.M) and propranolol (4 .mu.M) was present, but not in the absence of these drugs. In rabbit pulmonary artery a facilitatory effect of ACTH1-24 (0.1 .mu.M) was also observed when only cocaine (30 .mu.M) was present. ACTH1-24 (0.1 .mu.M) did not affect the S-I outflow of radioactivity from rat atria, rat pulmonary artery or guinea-pig pulmonary artery, either in the presence or in the absence of the cocktail containing corticosterone (40 .mu.M), cocaine (30 .mu.M) and propranolol (4 .mu.M). These results suggest that the presence of facilitatory rejunctional ACTH receptors may be restricted to rabbit sympathetic nerve endings. Angiotensin II (0.01 .mu.M), but not isoprenaline (0.1 .mu.M) or ACTH1-24 (0.1 .mu.M), significantly enhanced the S-I outflow of radioactivity from rabbit pulmonary artery. In the presence of phentolamine (1 .mu.M) to block inhibitory .alpha.2-adrenoceptors, the facilitatory effect of angiotensin II (0.01 .mu.M) was significantly enhanced, and a significant facilitatory effect of isoprenaline (0.1 .mu.M) and of ACTH1-24 (0.1 .mu.M) was then revealed. These results suggest that feedback inhibition of noradrenaline release, mediated through the prejunctional .alpha.2-adrenoceptor mechanism, buffers increases in noradrenaline release during activation of facilitatory prejunctional receptors. In rabbit pulmonary artery, two concentrations of 8-Br-cyclic AMP, (270 or 540 .mu.M), enhanced the S-I outflow of radioactivity in the presence of phenotalamine (1 .mu.M) to a similar extent. In the presence of 8-Br-cyclic AMP (270 .mu.M) and phentolamine, the facilitatory effects of isoprenaline (0.1 .mu.M) and of ACTH1-24 (0.1 .mu.M) were blocked, whereas that of angiotensin II (0.01 .mu.M) was not changed. These results suggest that both prejunctional .beta.-adrenoceptors and ACTH receptors enhanced noradrenaline release by generating cyclic AMP. The mechanism by which angiotensin II facilitates noradrenaline release is probably independent of the cyclic AMP second messenger pathway.