Terbutaline, forskolin and cAMP reduce secretion of aqueous humour in the isolated bovine eye.
Terbutaline, forskolin and cAMP reduce secretion of aqueous humour in the isolated bovine eye.
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DOI：
10.1371/journal.pone.0244253
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Delamere NA
中科院分区：
文献类型：
--
作者：
Shahidullah M;Wilson WS;Rafiq K;Sikder MH;Ferdous J;Delamere NA
为了阐明cAMP和细胞内Ca ~（2+）~（[Ca ~（2+）]i在调节房水形成（AHF）中的作用，我们研究了特布他林（terbutaline）、毛喉素（forskolin）和8-Br-cAMP对离体牛眼的影响。我们还研究了cAMP对培养的睫状体上皮（CE）细胞中钙信号的相互作用。用荧光素稀释法测定药物对AHF的作用。用Fura-2荧光比值法研究药物对[Ca ~（2+）]i的影响。特布他林（100 nmol-100 M）、毛喉素（30 nM-100 M）或8-Br-cAMP（100 nM- 10 μM）在动脉灌注液中给药可显著降低AHF。选择性蛋白激酶A抑制剂KT-5720可阻断特布他林降低AH的作用。ATP（100 M）引起[Ca 2 +]i快速、短暂（峰值）增加，随后出现持续5分钟以上的持续平台期。用特布他林、毛喉素或8-Br-cAMP预孵育细胞（6 min），可显著降低对ATP的峰值钙反应。另一方面，反应的持续平台期被每种药物增强。KT-5720可部分逆转特布他林对峰的抑制作用，完全抑制其对平台期的抑制作用。这些数据表明：（a）牛眼中的AHF可以通过环AMP操纵，通过蛋白激酶A起作用，（B）蛋白激酶A可以影响[Ca 2 +]i稳态，（c）从细胞内储存的钙释放，而不是进入，影响AHF，和（d）[Ca 2 +]i与cAMP的相互作用在调节AH分泌中起作用。
In order to elucidate involvement of cyclic AMP and intracellular Ca2+,[Ca2+]i, in the modulation of aqueous humour formation (AHF), we studied the effects of terbutaline, forskolin and 8-Br-cAMP in the isolated bovine eye. We also studied the interaction of cAMP on calcium signaling in cultured ciliary epithelial (CE) cells. Drug effects on AHF were measured by fluorescein dilution. Drug effects on [Ca2+]i were studied by the fura-2 fluorescence ratio technique. Terbutaline (100 nmol-100 M), forskolin (30 nM-100 M) or 8-Br-cAMP (100 nM– 10 μM), administered in the arterial perfusate produced significant reductions in AHF. The AH reducing effect of terbutaline was blocked by a selective inhibitor of protein kinase A (KT-5720). ATP (100 M) caused a rapid, transient (peak) increase in [Ca2+]i followed by a sustained plateau phase lasting more than 5 minutes. Preincubation of the cells (6 min) with terbutaline, forskolin or 8-Br-cAMP significantly reduced the peak calcium response to ATP. The sustained plateau phase of the response, on the other hand, was augmented by each of the agents. KT-5720 partially reversed the inhibitory effect of terbutaline on the peak and totally inhibited its effect on the plateau phase. These data indicate: (a) that AHF in the bovine eye can be manipulated through cyclic AMP, operating via protein kinase A, (b) that protein kinase A can affect [Ca2+]i homeostasis, (c) that calcium release from the intracellular store, not the entry, affects AHF, and (d) that interaction of [Ca2+]i with cAMP plays a role in modulating AH secretion.
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影响因子：
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作者：
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通讯作者：
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作者：
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