The effect of forskolin on the teratogenicity of methylxanthines in the chick embryo heart.
Interactions between forskolin and methylxanthines, including caffeine and isobutylmethylxanthine (IBMX), in the developing chick embryo heart were investigated. Forskolin, a potent activator of adenylate cyclase, was administered to young chick embryos (Hamburger-Hamilton stage 24) together with caffeine or IBMX at doses where each agent alone caused minimal embryotoxicity. The incidence of malformation in the embryonic chick heart or aorta induced by caffeine (5 x 10(-7) or 5 x 10(-6) mol) and IBMX (1 or 2.5 x 10(-6) mol) significantly increased with coadministration of forskolin (1 x 10(-9) mol). Cardiovascular malformations included ventricular septal defect, double outlet right ventricle, and aortic arch anomalies. These results indicate that forskolin potentiates the teratogenicity of caffeine or IBMX on the cardiovascular system in the chick embryo and suggest that this potentiation may be related to increase intracellular cAMP due to stimulation of adenylate cyclase (forskolin) and inhibition of phosphodiesterase (methylxanthines).
Nishikawa
T
T
Department of Pathology, Tokyo Women's Medical College, Japan.
Ishiyama
S
S
Takeda
K
K
Kasajima
T
T
D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage / Q000633:toxicity*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000196:embryology; D002110:Caffeine / Q000008:administration & dosage / Q000633:toxicity*; D002642:Chick Embryo; D005576:Colforsin / Q000008:administration & dosage / Q000633:toxicity*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000401:mortality; D010726:Phosphodiesterase Inhibitors / Q000633:toxicity; D015996:Survival Rate
D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D002110:Caffeine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine