Modulation of forskolin-mediated adenylyl cyclase activation by constitutively active G(S)-coupled receptors.
In transfected CHO cells constitutively active histamine H2 receptors not only increase the basal cAMP level, but also enhance forskolin-induced cAMP production. The increased forskolin response was inhibited by inverse H2 agonists with potencies similar to those determined at basal levels. The modulation of the forskolin response was also observed after H2 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.
Alewijnse
A E
AE
Leiden/Amsterdam Center for Drug Research, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Smit
M J
MJ
Rodriguez Pena
M S
MS
Verzijl
D
D
Timmerman
H
H
Leurs
R
R
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D005576:Colforsin / Q000494:pharmacology*; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D011970:Receptors, Histamine H2; D005576:Colforsin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases