Matsunaga T, Miyamoto K, Koshiura R
J Pharmacobiodyn. 1986 Sep;9(9):771-7. doi: 10.1248/bpb1978.9.771.
The treatment of AH130 cells with isoproterenol (IPN) resulted in an increase in the activity of cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase with a low Km value and a decrease in IPN-stimulated activity of adenylate cyclase. The activity of cyclic AMP phosphodiesterase was increased by IPN in a dose-dependent manner and reached a maximal increase at 30 min after the addition of 10(-4)M IPN. The addition of mitomycin C (MMC) at 15 min after the initiation of the treatment with IPN inhibited the increase in the activity of cyclic AMP phosphodiesterase in a dose-dependent manner. The extent of the development of desensitization, which was observed as a decrease in IPN-stimulated activity of adenylate cyclase, was dependent on the treatment time with IPN and the concentration of IPN. Desensitization was also observed as a decrease in prostaglandin E1-stimulated activity but not in basal and NaF-stimulated activity. The combined treatment with IPN and MMC showed a higher IPN-stimulated activity of adenylate cyclase than with a single treatment with IPN. This effect resulted from the enhancement of IPN-stimulated activity of the enzyme by MMC itself. These results show that the treatment of AH130 cells with IPN caused an induction of cyclic AMP phosphodiesterase and the development of desensitization of adenylate cyclase. Since the combined treatment with MMC inhibited both phenomena, the high intracellular cyclic AMP level appeared to be maintained by the combined treatment for a longer term than by a single treatment with IPN.
用异丙肾上腺素（IPN）处理AH130细胞，导致具有低Km值的环磷酸腺苷（环AMP）磷酸二酯酶活性增加，同时IPN刺激的腺苷酸环化酶活性降低。IPN以剂量依赖性方式增加环AMP磷酸二酯酶的活性，在加入10(-4)M IPN后30分钟达到最大增加。在用IPN处理开始15分钟后加入丝裂霉素C（MMC），以剂量依赖性方式抑制环AMP磷酸二酯酶活性的增加。脱敏的发展程度，表现为IPN刺激的腺苷酸环化酶活性降低，取决于IPN的处理时间和IPN的浓度。在前列腺素E1刺激的活性降低中也观察到脱敏，但在基础和NaF刺激的活性中未观察到。与单独用IPN处理相比，IPN和MMC联合处理显示出更高的IPN刺激的腺苷酸环化酶活性。这种效应是由于MMC本身增强了IPN刺激的该酶活性。这些结果表明，用IPN处理AH130细胞会诱导环AMP磷酸二酯酶并导致腺苷酸环化酶脱敏。由于MMC联合处理抑制了这两种现象，与单独用IPN处理相比，联合处理似乎能在更长时间内维持较高的细胞内环AMP水平。
