Martz A, Thomas M L
Biochem Pharmacol. 1983 Nov 15;32(22):3429-33. doi: 10.1016/0006-2952(83)90372-6.
Forskolin (FSK), an activator of adenylate cyclase in many tissues, was investigated to determine its potential for studying cyclic AMP-mediated, physiological events in bone. Tibiae from 14-day chick embryos were cultured in modified Eagle's medium for up to 8 hr, and the cyclic AMP and Ca2+ efflux responses to parathyroid hormone (PTH) and FSK were observed. FSK caused a concentration-related increase in tissue cyclic AMP, with 10(-6) M FSK producing a cyclic AMP response of similar magnitude to that elicited by 10(-6) M PTH (1-34). However, while 10(-6) M PTH was the maximally-activating PTH concentration, a further elevation was produced by 10(-5) M FSK. Chick embryo tibiae cultured for 8 hr in the presence of PTH exhibited a concentration-related stimulation of Ca2+ efflux up to 10(-6) M PTH. When this physiological effect was examined in bones cultured in the presence of FSK, a biphasic response to increasing FSK concentrations was found; Ca2+ efflux was stimulated by 10(-6) M and 3 X 10(-6) M FSK, but not by 10(-7) M or 10(-5) M FSK. In summary, concentrations of FSK, which produced tissue cyclic AMP accumulation similar to that produced by physiologically effective PTH concentrations, also resulted in net Ca2+ efflux from bone. These results indicate that FSK may be a useful agent for studying the role of cyclic AMP in the response of bone to hormones.
福斯高林（FSK）是许多组织中腺苷酸环化酶的激活剂，对其在研究骨中由环磷酸腺苷（cAMP）介导的生理事件的潜力进行了研究。将14日龄鸡胚的胫骨在改良的伊格尔培养基中培养长达8小时，观察对甲状旁腺激素（PTH）和FSK的环磷酸腺苷和钙离子外流反应。FSK导致组织中环磷酸腺苷浓度呈浓度依赖性增加，10^(-6) M FSK产生的环磷酸腺苷反应幅度与10^(-6) M PTH（1 - 34）引起的相似。然而，虽然10^(-6) M PTH是最大激活PTH浓度，但10^(-5) M FSK产生了进一步的升高。在PTH存在下培养8小时的鸡胚胫骨，对高达10^(-6) M PTH表现出浓度依赖性的钙离子外流刺激。当在FSK存在下培养的骨骼中检查这种生理效应时，发现对FSK浓度增加有双相反应；10^(-6) M和3×10^(-6) M FSK刺激钙离子外流，但10^(-7) M或10^(-5) M FSK则无此作用。总之，产生与生理有效PTH浓度相似的组织环磷酸腺苷积累的FSK浓度，也导致骨中钙离子净外流。这些结果表明，FSK可能是研究环磷酸腺苷在骨对激素反应中作用的有用试剂。
