Endothelin B receptor mediates ET-1 effects on cAMP and PGE2 accumulation in rat IMCD.
Endothelin B receptor mediates ET-1 effects on cAMP and PGE2 accumulation in rat IMCD.
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内皮素 B 受体介导 ET-1 对大鼠 IMCD 中 cAMP 和 PGE2 积累的影响。
DOI：
10.1152/ajprenal.1993.265.5.f670
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Hughes,AK
中科院分区：
文献类型：
--
作者：
Kohan,DE;Padilla,E;Hughes,AK
内皮素（ET）能有效抑制精氨酸抗利尿素（AVP）诱导的3′，5′-环单磷酸腺苷（cAMP）在髓内集管（IMCD）中的积累和na - k -腺苷三磷酸酶（na - k - atp酶）的活性。ET受体至少存在两种类型：ETA[结合ET-1 > ET-3 = sarafotoxin S6c (S6c)]和ETB（结合ET-1 = ET-3 = S6c）。我们研究了这些受体在新分离的大鼠IMCD细胞中介导ET的生物学作用。结合研究显示125I-ET-3被ET-1、ET-3和S6c置换，而125I-ET-1被ET-1 >> ET-3 = S6c置换。总之，这些研究证实了在IMCD中存在具有ETA和ETB结合特征的受体。ET-1、ET-3和S6c在减少avp刺激的cAMP积累方面具有同等的作用。BQ-123在选择性ETA受体拮抗剂浓度下，不改变ET-1、ET-3或S6c的作用。百日咳毒素或蛋白激酶C阻断，但吲哚美辛不抑制ET-1和S6c对avp刺激的cAMP积累的影响，这与激活相同的信号转导途径一致。ET-1和S6c在减少福斯克林刺激的cAMP积累方面是同等有效的，排除了抑制avp受体相互作用作为共同作用机制的可能性。最后，ET-1、ET-3和S6c引起类似的前列腺素E2 （PGE2）积累刺激，BQ-123不能阻断这一作用。这些数据表明，etb样受体介导ET刺激PGE2和抑制avp增强的cAMP在IMCD中的积累。eta样受体在IMCD中的功能仍有待确定。
Endothelin (ET) potently inhibits arginine vasopressin (AVP)-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and Na-K-adenosinetriphosphatase (Na-K-ATPase) activity in the inner medullary collecting duct (IMCD). At least two types of ET receptors exist: ETA [binds ET-1 > ET-3 = sarafotoxin S6c (S6c)] and ETB (binds ET-1 = ET-3 = S6c). We examined which of these receptors mediates biological actions of ET in freshly isolated rat IMCD cells. Binding studies revealed comparable displacement of 125I-ET-3 by ET-1, ET-3, and S6c, whereas 125I-ET-1 was displaced by ET-1 >> ET-3 = S6c. Together, these studies confirm the presence of receptors in the IMCD with ETA and ETB binding characteristics. ET-1, ET-3, and S6c were equipotent in reducing AVP-stimulated cAMP accumulation. BQ-123, at concentrations selective for ETA receptor antagonism, did not alter the effect of ET-1, ET-3, or S6c. Pertussis toxin or protein kinase C blockade, but not indomethacin, inhibited the effect of ET-1 and S6c on AVP-stimulated cAMP accumulation, consistent with activation of the same signal transduction pathways. ET-1 and S6c were equipotent in reducing forskolin-stimulated cAMP accumulation, ruling out inhibition of AVP-receptor interaction as a common mechanism of action. Finally, ET-1, ET-3, and S6c caused comparable stimulation of prostaglandin E2 (PGE2) accumulation, an effect that was not blocked by BQ-123. These data indicate that an ETB-like receptor mediates ET stimulation of PGE2 and inhibition of AVP-enhanced cAMP accumulation in the IMCD. The function of the ETA-like receptor in the IMCD remains to be determined.