title: Effects of forskolin on bone. Stimulation of cyclic AMP accumulation and calcium efflux from chick embryo tibiae in organ culture.
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.
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002642:Chick Embryo; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology; D013977:Tibia
chemical_list: D004224:Diterpenes; D010281:Parathyroid Hormone; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium