Bonilla-Felix M, John-Phillip C
Department of Pediatrics, University of Texas Health Science Center at Houston 77030.
Am J Physiol. 1994 Jul;267(1 Pt 2):F44-8. doi: 10.1152/ajprenal.1994.267.1.F44.
The immature kidney is characterized by resistance to arginine vasopressin (AVP). In the immature cortical collecting duct (iCCD), AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation is decreased, but the mechanisms involved are not known. We examined cAMP production in isolated CCD from immature and mature rabbits. Cellular cAMP levels were measured by radioimmunoassay under basal conditions and after stimulation with hormone. Basal cAMP production in the iCCD was not different from that in the mature CCD (mCCD). In contrast, AVP- and forskolin-stimulated cAMP generation were severely decreased in the iCCD. Inhibition of endogenous prostaglandin production by indomethacin increased AVP-stimulated cAMP generation in the iCCD to levels that were not different from the mCCD. Inhibition of protein kinase C (PKC) by staurosporine and inhibition of Gi by pertussis toxin elicited a mature cAMP response in the iCCD. These data suggest that the defect in AVP-stimulated cAMP production in the iCCD is mediated by prostaglandins via 1) activation of Gi and 2) direct inhibition of the adenylyl cyclase catalytic subunit. In addition, PKC appears to play a significant role.
未成熟肾脏的特点是对精氨酸加压素（AVP）有抵抗性。在未成熟的皮质集合管（iCCD）中，AVP刺激的腺苷3',5'-环磷酸（cAMP）生成减少，但其涉及的机制尚不清楚。我们检测了来自未成熟和成熟兔子的分离集合管中的cAMP生成情况。在基础条件下以及用激素刺激后，通过放射免疫测定法测量细胞内cAMP水平。iCCD中的基础cAMP生成与成熟集合管（mCCD）中的无差异。相比之下，iCCD中AVP和福斯高林刺激的cAMP生成严重减少。吲哚美辛抑制内源性前列腺素生成可使iCCD中AVP刺激的cAMP生成增加至与mCCD无差异的水平。星形孢菌素抑制蛋白激酶C（PKC）以及百日咳毒素抑制Gi可使iCCD产生成熟的cAMP反应。这些数据表明，iCCD中AVP刺激的cAMP生成缺陷是由前列腺素通过以下方式介导的：1）激活Gi；2）直接抑制腺苷酸环化酶催化亚基。此外，PKC似乎发挥了重要作用。
