Proll M A, Clark R B, Butcher R W
Mol Cell Endocrinol. 1986 Mar;44(3):211-7. doi: 10.1016/0303-7207(86)90126-7.
Adenosine stimulates and inhibits adenylate cyclase activity and cAMP levels in WI-38 and VA13 fibroblasts. The inhibitory effects appear to be mediated by both A1 receptors and the P-site. Results supporting these conclusions are as follows: Adenosine by itself increased cAMP accumulation in these cells. PGE1-stimulated cAMP accumulation was inhibited by adenosine in a concentration-dependent fashion. IAP treatment blocked adenosine inhibition of cAMP accumulation and adenylate cyclase activity and enhanced adenosine stimulation of cAMP accumulation in VA13 cells. Theophylline and MIX attenuated adenosine inhibition of cAMP accumulation. Adenosine analogs with substitutions in the purine ring inhibited PGE1-stimulated cAMP accumulation and adenylate cyclase activity. PGE1-stimulated cAMP accumulation was inhibited by the P-site agonist 2'5'-dideoxyadenosine, but this inhibition was not attenuated by MIX or IAP treatment. These data support the idea that adenosine may inhibit cAMP accumulation in VA13 or WI-38 cells by acting at an A1 receptor of the P-site. The decrease in cAMP accumulation mediated by the A1 receptor appeared to be due at least in part to an Ni-mediated inhibition of adenylate cyclase.
腺苷可刺激并抑制WI - 38和VA13成纤维细胞中的腺苷酸环化酶活性及环磷酸腺苷(cAMP)水平。其抑制作用似乎是由A1受体和P位点共同介导的。支持这些结论的结果如下:腺苷本身可增加这些细胞中cAMP的积累。腺苷以浓度依赖的方式抑制前列腺素E1(PGE1)刺激的cAMP积累。IAP处理可阻断腺苷对VA13细胞中cAMP积累和腺苷酸环化酶活性的抑制作用,并增强腺苷对cAMP积累的刺激作用。茶碱和MIX可减弱腺苷对cAMP积累的抑制作用。嘌呤环上有取代基的腺苷类似物可抑制PGE1刺激的cAMP积累和腺苷酸环化酶活性。P位点激动剂2'5'-二脱氧腺苷可抑制PGE1刺激的cAMP积累,但MIX或IAP处理并不能减弱这种抑制作用。这些数据支持这样一种观点,即腺苷可能通过作用于P位点的A1受体来抑制VA13或WI - 38细胞中cAMP的积累。由A1受体介导的cAMP积累的减少似乎至少部分是由于Ni介导的腺苷酸环化酶抑制作用。