Comparison of second-messenger responses to muscarinic receptor stimulation in M1-transfected A9 L cells.
A9 L cells stable transfected with m1 muscarinic receptors were stimulated with the full agonist carbachol and with the partial agonist pilocarpine. The EC50 values and maximal activation from PI hydrolysis, calcium mobilization, membrane hyperpolarization, cell proliferation and arachidonic acid release were compared. Pilocarpine was approximately half as effective in eliciting PI hydrolysis, calcium mobilization and arachidonic acid release, but was almost as effective as carbachol in the other assays. These findings suggest that the intracellular signals leading to receptor-mediated cell proliferation and to membrane hyperpolarization are amplified, and that therefore these assays are not suitable for determining whether a compound is a partial agonist.
Baumgold
J
J
Department of Radiology, George Washington University Medical Center, Washington, D.C. 20037, USA.
Dyer
K
K
Falcone
J F
JF
Bymaster
F P
FP
D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D010862:Pilocarpine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*; D014162:Transfection
D011976:Receptors, Muscarinic; D010862:Pilocarpine; D016718:Arachidonic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D002118:Calcium