Isoproterenol-stimulated renin secretion in the rat: second messenger roles of Ca and cyclic AMP.

Isoproterenol-stimulated renin secretion in the rat: second messenger roles of Ca and cyclic AMP.
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异丙肾上腺素刺激大鼠肾素分泌:Ca 和环 AMP 的第二信使作用。

DOI:
10.1016/0024-3205(82)90694-4
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发表时间:
1982
期刊:
影响因子:
6.1
通讯作者:
Churchill,MC
Churchill,MC
中科院分区:
医学2区
文献类型:
--
作者:
Churchill,PC;Churchill,MC

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这些实验旨在阐明两个第二信使(环状 3'、5' 腺苷单磷酸 [c-AMP];细胞内钙 [Cai])中哪一个与肾素分泌过程更密切相关。使用大鼠肾皮质切片制剂。先前显示通过增加Cai(哇巴因、钒酸盐、血管紧张素II、抗利尿激素和60 mM K)抑制基础肾素分泌的药物拮抗和/或阻断异丙肾上腺素刺激的分泌,这被认为是由腺苷酸环化酶激活和c-AMP水平增加介导的。二丁酰c-AMP的刺激作用被拮抗和/或阻断异丙肾上腺素刺激的分泌的相同试剂拮抗和/或阻断。因此,这些药物对异丙肾上腺素刺激的分泌的抑制作用不能用 Ca 诱导的 c-AMP 产生减少来解释。有效的磷酸二酯酶抑制剂(3-异丁基-1-甲基黄嘌呤)刺激分泌率。其与二丁酰 c-AMP 的组合产生了更大的刺激。哇巴因阻断了这种组合的刺激作用。这些结果与 c-AMP 和肾素分泌率之间不变的直接关系不一致,但与 Cai 和肾素分泌之间的反比关系一致。此外,它们与以下假设一致:在异丙肾上腺素刺激的肾素分泌中,c-AMP是第二信使,而Cathe是第三信使或最后信使。
These experiments were designed to elucidate which of two second messengers (cyclic 3', 5' adenosine monophosphate [c-AMP]; intracellular calcium [Cai]) was more closely related to the renin secretory process. The rat renal cortical slice preparation was used. Agents which previously were shown to inhibit basal renin secretion by increasing Cai(ouabain, vanadate, angiotensin II, antidiuretic hormone, and 60 mM K) antagonized and/or blocked isoproterenol-stimulated secretion, which is thought to be mediated by adenylate cyclase activation and increased levels of c-AMP. The stimulatory effect of dibutyryl c-AMP was antagonized and/or blocked by the same agents which antagonized and/or blocked isoproterenol-stimulated secretion. Thus, the inhibitory effects of these agents on isoproterenol-stimulated secretion cannot be explained by a Ca-induced decrease in c-AMP production. Secretory rate was stimulated by a potent phosphodiesterase inhibitor (3-isobutyl-l-methylxanthine). A combination of this and dibutyryl c-AMP produced even greater stimulation. Ouabain blocked the stimulatory effect of this combination. These results are not consistent with an invariant direct relationship between c-AMP and renin secretory rate, but are consistent with an inverse relationship between Caiand renin secretion. Further, they are consistent with the sypothesis that in isoproterenol-stimulated renin secretion, c-AMP is the second and Caithe third or the final messenger.
DOI: 10.1111/j.1476-5381.1974.tb09599.x
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