Stimulation by forskolin of the thyroid adenylate cyclase, cyclic AMP accumulation and iodine metabolism.
Forskolin, a diterpene hypotensive drug, activates adenylate cyclase in brain and in some other tissues (Seamon et al., 1981). Forskolin activated adenylate cyclase in particulate preparations and enhanced cyclic AMP accumulation in slices of dog thyroid. These effects were maximal within minutes and remained constant afterwards. The action of forskolin on intact cells disappeared rapidly after washing. It reproduced two known cyclic AMP-mediated TSH effects: the activation of secretion and of protein iodination. Forskolin thus provides a very convenient tool for the study of the action of defined elevations of cyclic AMP level in thyroid cells. The activation by forskolin of adenylate cyclase was not reduced by Mn2+ which uncouples TSH and PGE1 action. This suggests that in the thyroid also, forskolin acts beyond the receptor level. The effect of forskolin on cyclic AMP accumulation was inhibited by the known negative regulators of this system in the thyroid, acetylcholine, iodide, norepinephrine, PGF1 alpha and adenosine. On the other hand, forskolin potentiated the effects of TSH, PGE1 and cholera toxin. These data show that, though it does not require the receptors for its action, forskolin does not uncouple them from the catalytic unit of adenylate cyclase.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007455:Iodine / Q000378:metabolism*; D007700:Kinetics; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology
D004224:Diterpenes; D005576:Colforsin; D013972:Thyrotropin; D007455:Iodine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases