Lower efficacy: interaction with an inhibitory receptor or partial agonism?
It is very common in practice to find that some concentration-response curves are 'bell shaped', and this phenomenon also applies to partial agonist curves. On the basis of these considerations, a mathematical model has been developed for the interaction of a ligand with two different receptors that mediate opposite effects (one stimulatory and one inhibitory), and is discussed in this article by Enrico Rovati and Simonetta Nicosia. This model can account for both an apparent reduction in efficacy and the curvature of the upper plateau of some concentration-response curves. Therefore, under certain conditions, an agonist that also interacts with an inhibitory receptor might be mistaken for a partial agonist, unless the concentration-response curves are performed over the widest possible range of concentrations.
Rovati
G E
GE
Laboratory of Molecular Pharmacology, University of Milan, Italy.
Nicosia
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D008024:Ligands; D016015:Logistic Models; D008956:Models, Chemical; D009130:Muscle, Smooth / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*
D008024:Ligands; D011453:Prostaglandins; D000644:Quaternary Ammonium Compounds; D011956:Receptors, Cell Surface; D000262:Adenylyl Cyclases