Inhibition of cAMP formation by EGF in thyroid follicles is mediated by intracellular Ca++.
The mechanism of cAMP-inhibition by EGF was studied in isolated porcine thyroid follicles. EGF inhibited TSH-induced cAMP-formation maximally by 40%, this effect remained up to 1 h of pre-incubation. The calcium-ionophore A 23 187 also inhibited cAMP-formation, but its effect was relieved after 1 h. The phorbolester TPA had a biphasic influence on cAMP-formation, with a transient increase (5 min) before a sustained inhibition (60 min); the inhibitory effect was mimicked by the diacylglycerol 1-oleoyl-2-acetyl-glycerol. Exogenous arachidonic acid had only a small and transient inhibitory effect on cAMP-formation. We conclude, that EGF inhibits cAMP-formation by a raise of intracellular Ca++, as well as by the direct activation of proteinkinase C, indicating, that a phosphorylated product could be a mediator for the inhibition of adenylate cyclase.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007700:Kinetics; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*
D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D002118:Calcium