Frelin C, Breittmayer J P, Vigne P
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique 660, Valbonne, France.
J Biol Chem. 1993 Apr 25;268(12):8787-92.
The action of adenine and uracyl nucleotides on rat brain capillary endothelial cells was investigated. ATP, UTP, and adenosine 5'-O-(3-thiotrisphosphate) activated phospholipase C and induced large increases in [Ca2+]i. ADP had a different action. At low concentrations (< 10 microM), ADP induced the mobilization of a thapsigargin-sensitive intracellular Ca2+ store in the absence of measurable production of inositol phosphates. At larger concentrations (> 30 microM), ADP activated phospholipase C. The actions of ATP and ADP and of UTP and ADP were additive. Those of ATP and UTP were not. In the presence of ATP or UTP, the dose-response curve for ADP action on [Ca2+]i was monophasic and corresponded to the high affinity responses. Finally, we observed that ADP did not desensitize cells to the actions of ATP and UTP. In contrast, cross-desensitization of the actions of ATP and UTP were observed. It is concluded that two types of receptors account for the actions of nucleotides: (i) a nucleotide that recognizes ATP and UTP and that is positively coupled to phospholipase C; and (ii) an ADP-specific receptor that induces the mobilization of a thapsigargin-sensitive intracellular Ca2+ pool in a manner independent of the formation of inositol phosphates.
研究了腺嘌呤和尿嘧啶核苷酸对大鼠脑毛细血管内皮细胞的作用。ATP、UTP和腺苷5'-O-(3-硫代三磷酸)激活磷脂酶C并诱导细胞内钙离子浓度([Ca2+]i)大幅升高。ADP则有不同的作用。在低浓度(<10微摩尔)时，ADP在不产生可测量的肌醇磷酸的情况下诱导了毒胡萝卜素敏感的细胞内钙库的动员。在较高浓度(>30微摩尔)时，ADP激活磷脂酶C。ATP与ADP以及UTP与ADP的作用是相加的。而ATP与UTP的作用并非如此。在存在ATP或UTP的情况下，ADP对[Ca2+]i作用的剂量反应曲线是单相的，且对应于高亲和力反应。最后，我们观察到ADP不会使细胞对ATP和UTP的作用产生脱敏。相反，观察到ATP和UTP作用的交叉脱敏。结论是，核苷酸的作用由两种类型的受体介导：(i)一种识别ATP和UTP并与磷脂酶C正偶联的核苷酸受体；(ii)一种ADP特异性受体，它以独立于肌醇磷酸形成的方式诱导毒胡萝卜素敏感的细胞内钙池的动员。
