A1 and A2 adenosine receptors in rabbit cortical collecting tubule cells. Modulation of hormone-stimulated cAMP.
A1 and A2 adenosine receptors in rabbit cortical collecting tubule cells. Modulation of hormone-stimulated cAMP.
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兔皮质集合管细胞中的 A1 和 A2 腺苷受体。
DOI：
10.1172/jci112875
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Spielman,WS
中科院分区：
文献类型：
--
作者：
Arend,LJ;Sonnenburg,WK;Smith,WL;Spielman,WS
腺苷类似物用于研究腺苷改变肾小管功能的细胞机制。用5 ′-N-乙基甲酰胺腺苷（NECA）、N6-环己基腺苷（CHA）和R-N6-苯基异丙基腺苷（PIA）处理培养的兔皮质集合管（RCCT）细胞。所有这三种类似物都产生了剂量依赖性抑制和刺激RCCT细胞环AMP（cAMP）的产生。cAMP积累的刺激发生在0.1 μ M至100 μ M的类似物浓度下，效力的等级顺序为NECA大于PIA大于CHA。抑制发生在1 nM至1 μ M的浓度下，效力的等级顺序为CHA大于PIA大于NECA。1，3-二乙基-8-苯基黄嘌呤和异丁基甲基黄嘌呤可抑制cAMP的产生。CHA（50 nM）减弱AVP和异丙肾上腺素刺激的cAMP积累。百日咳毒素预处理的RCCT细胞，取消了这种调制的ESTA诱导cAMP的生产。前列腺素E2的产生不受0.1 mM CHA的影响。这些发现表明RCCT细胞中存在腺苷的抑制性（A1）和刺激性（A2）受体。此外，A1受体的占有率通过对腺苷酸环化酶系统的抑制性鸟嘌呤核苷酸结合调节组分Ni的作用导致基础和腺苷酸刺激的cAMP形成的抑制。
Adenosine analogs were used to investigate the cellular mechanisms by which adenosine may alter renal tubular function. Cultured rabbit cortical collecting tubule (RCCT) cells, isolated by immunodissection, were treated with 5'-N-ethylcarboxamideadenosine (NECA), N6-cyclohexyladenosine (CHA), and R-N6-phenylisopropyladenosine (PIA). All three analogs produced both dose-dependent inhibition and stimulation of RCCT cell cyclic AMP (cAMP) production. Stimulation of cAMP accumulation occurred at analog concentrations of 0.1 microM to 100 microM with the rank order of potency NECA greater than PIA greater than CHA. Inhibition occurred at concentrations of 1 nM to 1 microM with the rank order of potency CHA greater than PIA greater than NECA. These effects on cAMP production were inhibited by 1,3-diethyl-8-phenylxanthine and isobutylmethylxanthine. CHA (50 nM) blunted AVP- and isoproterenol-stimulated cAMP accumulation. This modulation of hormone-induced cAMP production was abolished by pretreatment of RCCT cells with pertussis toxin. Prostaglandin E2 production was unaffected by 0.1 mM CHA. These findings indicate the presence of both inhibitory (A1) and stimulatory (A2) receptors for adenosine in RCCT cells. Moreover, occupancy of the A1 receptor causes inhibition of both basal and hormone-stimulated cAMP formation through an action on the inhibitory guanine nucleotide-binding regulatory component, Ni, of the adenylate cyclase system.