Rouse D, Leite M, Suki W N
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Am J Physiol. 1994 Aug;267(2 Pt 2):F289-95. doi: 10.1152/ajprenal.1994.267.2.F289.
In rabbit renal cortical collecting tubule (CCT), perfused in vitro at 38 degrees C, ATP in concentrations of 10(-7) M and greater inhibits arginine vasopressin (AVP)-stimulated osmotic water permeability (Pf). The P1-purinergic receptor antagonist 8-phenyltheophylline did not attenuate the inhibitory action of ATP, and the poorly hydrolyzable ATP analogue, 5'-adenylylimidodiphosphate (AMP-PNP), mimicked the effect of ATP, arguing against an effect of ATP on a P1 receptor or the "P site." Purinergic receptor agonists inhibited AVP-stimulated Pf with the following rank order efficacy: ATP = ADP = UTP = AMP-PNP = alpha, beta-methylene-ATP > 2-methylthio-ATP >> AMP > adenosine, consistent with the pharmacology of a "nucleotide" receptor subtype. Pertussis toxin pretreatment attenuated the action of 10(-5) and 10(-6) MATP; however, 10(-4) MATP failed to inhibit the hydrosmotic action of forskolin or 8-bromoadenosine 3',5'-cyclic monophosphate. Pretreatment with the phosphodiesterase inhibitor RO20-1724 or indomethacin did not inhibit the action of ATP. Staurosporin and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester significantly attenuated the inhibition of Pf by lower concentrations of ATP. These data suggest that ATP activates nucleotide receptors on the CCT, mobilizing intracellular Ca2+, which inhibits the hydrosmotic action of AVP.
在38℃体外灌注的兔肾皮质集合管（CCT）中，浓度为10⁻⁷M及更高的ATP可抑制精氨酸加压素（AVP）刺激的渗透水通透性（Pf）。P1嘌呤能受体拮抗剂8-苯基茶碱并不能减弱ATP的抑制作用，而水解性差的ATP类似物5'-腺苷酰亚胺二磷酸（AMP-PNP）可模拟ATP的作用，这表明ATP对P1受体或“P位点”没有作用。嘌呤能受体激动剂抑制AVP刺激的Pf的效力顺序如下：ATP = ADP = UTP = AMP-PNP = α,β-亚甲基-ATP > 2-甲硫基-ATP >> AMP > 腺苷，这与一种“核苷酸”受体亚型的药理学特性一致。百日咳毒素预处理可减弱10⁻⁵M和10⁻⁶M ATP的作用；然而，10⁻⁴M ATP未能抑制福斯高林或8-溴腺苷3',5'-环一磷酸的水渗透性作用。用磷酸二酯酶抑制剂RO20-1724或吲哚美辛预处理并不能抑制ATP的作用。星形孢菌素和3,4,5-三甲氧基苯甲酸8-（二乙氨基）辛酯可显著减弱较低浓度ATP对Pf的抑制作用。这些数据表明，ATP激活CCT上的核苷酸受体，动员细胞内Ca²⁺，从而抑制AVP的水渗透性作用。
