Teitelbaum I
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Am J Physiol. 1993 Feb;264(2 Pt 2):F216-20. doi: 10.1152/ajprenal.1993.264.2.F216.
Studies were performed to identify the site at which activation of protein kinase C (PKC) inhibits arginine vasopressin (AVP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cultured rat inner medullary collecting tubule (RIMCT) cells. Neither endogenous stimulation of PKC by epidermal growth factor (EGF) nor the addition of exogenous 1,2-dioctanoyl-sn-glycerol (DOG) impaired forskolin-stimulated cAMP accumulation. Similarly, neither EGF nor DOG altered cAMP generation in response to cholera toxin. However, pretreatment of RIMCT cells with pertussis toxin resulted in loss of inhibition of AVP-stimulated cAMP accumulation by DOG. Likewise, the ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), to inhibit AVP-stimulated cAMP accumulation was eliminated by pretreatment with pertussis toxin. PMA also inhibited AVP-stimulated adenylyl cyclase activity in plasma membranes prepared from rat inner medullas. In contrast to its effects on AVP, activation of PKC did not impair cAMP accumulation in response to isoproterenol or prostaglandin E2. These studies demonstrate that PKC-mediated inhibition of AVP-stimulated cAMP accumulation in cultured RIMCT cells requires the intact inhibitory guanine nucleotide binding protein Gi.
开展了多项研究，以确定蛋白激酶C（PKC）激活后抑制精氨酸血管加压素（AVP）刺激的3',5'-环磷酸腺苷（cAMP）在培养的大鼠髓质内层集合管（RIMCT）细胞中积累的位点。表皮生长因子（EGF）对PKC的内源性刺激以及添加外源性1,2 - 二辛酰 - sn - 甘油（DOG）均未损害福斯高林刺激的cAMP积累。同样，EGF和DOG均未改变霍乱毒素刺激的cAMP生成。然而，用百日咳毒素预处理RIMCT细胞会导致DOG对AVP刺激的cAMP积累的抑制作用丧失。同样，佛波酯佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）抑制AVP刺激的cAMP积累的能力也因百日咳毒素预处理而消除。PMA还抑制了从大鼠髓质制备的质膜中AVP刺激的腺苷酸环化酶活性。与对AVP的作用相反，PKC的激活并未损害异丙肾上腺素或前列腺素E2刺激的cAMP积累。这些研究表明，PKC介导的对培养的RIMCT细胞中AVP刺激的cAMP积累的抑制作用需要完整的抑制性鸟嘌呤核苷酸结合蛋白Gi。
