A1 adenosine receptors inhibit chloride transport in the shark rectal gland. Dissociation of inhibition and cyclic AMP.
A1 adenosine receptors inhibit chloride transport in the shark rectal gland. Dissociation of inhibition and cyclic AMP.
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A1 腺苷受体抑制鲨鱼直肠腺中的氯离子转运。
DOI：
10.1172/jci114614
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
ForrestJr,JN
中科院分区：
文献类型：
--
作者：
Kelley,GG;Poeschla,EM;Barron,HV;ForrestJr,JN
在角鲨 (Squalus acanthias) 的体外灌注直肠腺中，腺苷类似物 2-氯腺苷 (2Clado) 完全可逆地抑制毛喉素刺激的氯化物分泌，IC50 为 5 nM。其他 A1 受体激动剂包括环己基腺苷 (CHA)、N-乙基甲酰胺腺苷 (NECA) 和 R-苯基异丙基腺苷 (R-PIA) 也完全抑制毛喉素刺激的氯离子分泌。 PIA 的“S”立体异构体 (S-PIA) 是毛喉素刺激的氯离子分泌的较弱抑制剂，与 PIA 立体异构体对 A1 受体的亲和力特征一致。腺苷受体拮抗剂8-苯基茶碱和8-环戊茶碱完全阻断2Clado抑制毛喉素刺激的氯离子分泌的作用。当在灌注腺体中同时测定氯化物分泌和组织环(c)AMP含量时，2Clado完全抑制分泌，但仅抑制毛喉素刺激的cAMP积累34-40%，表明2Clado抑制分泌的机制至少部分不依赖于cAMP。与这些结果一致，A1受体激动剂仅适度抑制(9-15%)毛喉素刺激的腺苷酸环化酶活性，并且2Clado显着抑制由渗透性cAMP类似物8-氯苯硫基cAMP (8CPT cAMP)刺激的氯分泌。这些发现为高亲和力 A1 腺苷受体抑制模型上皮细胞中激素刺激的离子转运提供了第一个证据。这种抑制的主要部分是通过独立于 cAMP 信使系统的机制发生的。
In the in vitro perfused rectal gland of the dogfish shark (Squalus acanthias), the adenosine analogue 2-chloroadenosine (2Clado) completely and reversibly inhibited forskolin-stimulated chloride secretion with an IC50 of 5 nM. Other A1 receptor agonists including cyclohexyladenosine (CHA), N-ethylcarboxamideadenosine (NECA) and R-phenylisopropyl-adenosine (R-PIA) also completely inhibited forskolin stimulated chloride secretion. The "S" stereoisomer of PIA (S-PIA) was a less potent inhibitor of forskolin stimulated chloride secretion, consistent with the affinity profile of PIA stereoisomers for an A1 receptor. The adenosine receptor antagonists 8-phenyltheophylline and 8-cyclopentyltheophylline completely blocked the effect of 2Clado to inhibit forskolin-stimulated chloride secretion. When chloride secretion and tissue cyclic (c)AMP content were determined simultaneously in perfused glands, 2Clado completely inhibited secretion but only inhibited forskolin stimulated cAMP accumulation by 34-40%, indicating that the mechanism of inhibition of secretion by 2Clado is at least partially cAMP independent. Consistent with these results, A1 receptor agonists only modestly inhibited (9-15%) forskolin stimulated adenylate cyclase activity and 2Clado markedly inhibited chloride secretion stimulated by a permeant cAMP analogue, 8-chlorophenylthio cAMP (8CPT cAMP). These findings provide the first evidence for a high affinity A1 adenosine receptor that inhibits hormone stimulated ion transport in a model epithelia. A major portion of this inhibition occurs by a mechanism that is independent of the cAMP messenger system.