Schulman G, Lindemeyer R, Barman A, Karnik S, Bastl C P
Department of Medicine, Temple University Health Sciences Center, Philadelphia, Pennsylvania 19140, USA.
J Clin Invest. 1996 Jul 1;98(1):157-66. doi: 10.1172/JCI118761.
Atrial natriuretic peptide (ANP) inhibits and aldosterone (ALDO) stimulates Na conductive transport. Therefore, the effects of ANP and its second messenger cGMP on mineralocorticoid receptor (MR) function in rat colon surface and crypt cells were examined. 100 nM 8-Br-cGMP decreased surface [3H]ALDO binding by 42 +/- 4% but increased crypt [3HvALDO binding by 52+/-16%. ANP decreased surface [3H]ALDO binding by approximately 50% after a 2.5-h lag period but had no effect on crypt ALDO binding. ANP and cGMP rapidly (< 15 min) inhibited surface cell ALDO-induced MR nuclear translocation but did not affect crypt MR nuclear translocation. Inhibition of cGMP-dependent protein kinase with KT5823 blocked the inhibitory effects of ANP and 8-Br-cGMP on surface cell ALDO binding and MR nuclear translocation. In crypt, KT5823 increased baseline [3H]ALDO binding but did not inhibit the stimulatory effect of exogenous cGMP. DEAE-cellulose chromatography and gel mobility shift assay showed that ANP did not inhibit surface MR activation. ANP inhibited ALDO stimulated short circuit current in distal colon. These data demonstrate cell-specific regulation of MR function. In surface cells, ANP rapidly inhibits MR nuclear translocation and ALDO-induced short circuit current. ANP inhibition of MR function may be an additional mechanism of ANP antagonism of Na reabsorption.
心房利钠肽（ANP）抑制而醛固酮（ALDO）刺激钠的传导性转运。因此，研究了ANP及其第二信使环磷酸鸟苷（cGMP）对大鼠结肠表面和隐窝细胞中盐皮质激素受体（MR）功能的影响。100 nM 8-溴-cGMP使表面[3H]ALDO结合减少42±4%，但使隐窝[3H]ALDO结合增加52±16%。ANP在延迟2.5小时后使表面[3H]ALDO结合减少约50%，但对隐窝ALDO结合无影响。ANP和cGMP迅速（<15分钟）抑制表面细胞中ALDO诱导的MR核转位，但不影响隐窝MR核转位。用KT5823抑制环磷酸鸟苷依赖性蛋白激酶可阻断ANP和8-溴-cGMP对表面细胞ALDO结合和MR核转位的抑制作用。在隐窝中，KT5823增加了基线[3H]ALDO结合，但不抑制外源性cGMP的刺激作用。二乙氨基乙基纤维素色谱法和凝胶迁移率变动分析表明，ANP不抑制表面MR激活。ANP抑制ALDO刺激的远端结肠短路电流。这些数据表明MR功能存在细胞特异性调节。在表面细胞中，ANP迅速抑制MR核转位和ALDO诱导的短路电流。ANP对MR功能的抑制可能是ANP拮抗钠重吸收的另一种机制。
