Cell-specific coupling of PGE2 to different transduction pathways in arginine vasopressin- and glucagon-sensitive segments of the rat renal tubule
Cell-specific coupling of PGE2 to different transduction pathways in arginine vasopressin- and glucagon-sensitive segments of the rat renal tubule
复制标题
DOI：
10.1038/sj.bjp.0702390
复制
发表时间：
1999-02-01
影响因子：
7.3
通讯作者：
Chabardès, D
中科院分区：
文献类型：
--
作者：
Aarab, L;Siaume-Perez, S;Chabardès, D
本研究的目的是探讨前列腺素E-2 （PGE(2)）抑制激素刺激的腺苷3′：5′-环单磷酸腺苷（环AMP）在大鼠肾细胞外髓集管（OMCD）和髓厚升肢（MTAL）中积累的转导途径在OMCD中，0.3 μ M的PGE(2)和低浓度的Ca2+离子载体（10 nM离子霉素或50 nM A23187）通过相同的过程抑制约50%的精氨酸抗压素（AVP）刺激的环AMP含量舒prostone是一种PGE(2)受体EP1/EP3亚型的激动剂，可降低OMCD和MTAL样品中avp依赖性环AMP的积累。引起半最大抑制的浓度在OMCD中约为50 nM，在MTAL中约为0.1 nM。4在MTAL中，1 nM的磺胺酮和PGE(2)通过ptx敏感、Ca2+独立的途径抑制了约90%的avp依赖性环AMP含量在OMCD中，PGE(2)通过对PTX和Ca2+无关的过程敏感，减少了约50%胰高血糖素依赖性环AMP的合成。舒前列酮1nm对细胞的抑制作用相同这些结果表明，PGE(2)通过G α 1介导的MTAL细胞和OMCD的胰高血糖素敏感细胞中腺苷酸环化酶活性的抑制，或通过在OMCD的avp敏感细胞中ptx不敏感的细胞内Ca2+浓度的增加，减少激素依赖性环AMP的积累。
1 The aim of the present study was to investigate the transduction pathways elicited by prostaglandin E-2 (PGE(2)) to inhibit hormone-stimulated adenosine 3 ':5 '-cyclic monophosphate (cyclic AMP) accumulation in the outer medullary collecting duct (OMCD) and medullary thick ascending limb (MTAL) microdissected from the rat nephron.2 In the OMCD, 0.3 mu M PGE(2) and low concentrations of Ca2+ ionophores (10 nM ionomycin or 50 nM A23187) inhibited by about 50% a same pool of arginine vasopressin (AVP)-stimulated cyclic AMP content through a same process insensitive to Bordetella pertussis toxin (PTX).3 Sulprostone, an agonist of the EP1/EP3 subtypes of the PGE(2) receptor, decreased AVP-dependent cyclic AMP accumulation in OMCD and MTAL samples. The concentration eliciting half-maximal inhibition was of about 50 nM in OMCD and 0.1 nM in MTAL.4 In MTAL, 1 nM sulprostone and PGE(2) inhibited by about 90% a same pool of AVP-dependent cyclic AMP content through a PTX-sensitive, Ca2+-independent pathway.5 In the OMCD, PGE(2) decreased by about 50% glucagon-dependent cyclic AMP synthesis by a process sensitive to PTX and Ca2+-independent. Sulprostone 1 nM induced the same level of inhibition.6 These results demonstrate that PGE(2) decrease hormone-dependent cyclic AMP accumulation through a G alpha i-mediated inhibition of adenylyl cyclase activity in MTAL cells and glucagon-sensitive cells of the OMCD or through a PTX-insensitive increase of intracellular Ca2+ concentration in AVP-sensitive cells of the OMCD.