Effects of forskolin on bone. Stimulation of cyclic AMP accumulation and calcium efflux from chick embryo tibiae in organ culture |
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Authors: | A Martz M L Thomas |
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Affiliation: | Department of Pharmacology, School of Medicine, University of Missouri, Columbia, MO 65212, U.S.A. |
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Abstract: | 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. |
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Keywords: | Send correspondence to: Dr. Mary L. Thomas Department of Pharmacology and Toxicology University of Texas Medical Branch Galveston TX 77550. |
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