Modulation of forskolin-mediated adenylyl cyclase activation by constitutively active GS-coupled receptors

In transfected CHO cells constitutively active histamine H-2 receptors not only increase the basal cAMP level, but also enhance forskolin-induced cAMP production. The increased forskolin response was inhibited by inverse H-2 agonists with potencies similar to those determined at basal levels. The modulation of the forskolin response was also observed after H-2 receptor expression in HEK-293 and Sf9 cells or TSH receptor expression in COS-7 cells, The enhancement of forskolin-induced cAMP production seems to be a general characteristic of constitutively active G(s)-coupled receptors and can be very useful to study inverse agonism at wild-type receptors. (C) 1997 Federation of European Biochemical Societies.