Whereby any differences in stoichiometry of the receptor, G proteins and other signalling molecules may be anticipated to affect agonist affinity, this discrepancy may reflect differences in the G protein coupling of the CB2 receptors between native and heterologous expression systems. R,S AM1241 restricted cAMP generation stimulated by treatment of the h CB2 expressing cell line with 1 mM forskolin, consistent with this racemate working as an agonist of hCB2 receptors. The concentration used in our studies was lower than those used in a similar study, whereby it was reported that the event of R,S AM1241 in CTEP cyclase assays was vulnerable to the concentration of forskolin used to encourage hCB2 expressing cells. In our characterization of the mouse receptors, R,S AM1241 confirmed inverse agonist homes at the same concentration of forskolin that has been related to agonist action at the hCB2 receptors. S AM1241 was seen to be an agonist at mouse, human and rat CB2 receptors, whereas Dtc AM1241 was observed to be an agonist at the human receptor and an inverse agonist in the cells with the mouse receptors. The functional properties of the racemate are dominated by those of the R enantiomer, Metastasis showing its over 40 fold higher CB2 affinity weighed against the S enantiomer. In an evaluation of racemic AM1241 in hCB2 receptor assays, functional task varied depending on the end point that was measured. As a case of protean agonism, a trend when the state of constitutive receptor activity can determine the functional impact of a ligandreceptor interaction the authors recommended the various functional results of R,S AM1241. Beneath the protean agonist theory, two receptor states, a ligand bound and a constitutively active, ligand unbound kind, participate for G proteins. In the event the efficacy of the constitutively active receptor is higher-than that of the ligand bound receptor, then a protean agonist, by causing a less active receptor conformation, will be as an inverse agonist. In the absence of constitutive activity, the exact same ligand can act as a partial agonist. Differing degrees of receptor activation in numerous cell based assay systems may hence suffice to produce different practical outcomes. It is tempting, therefore, to imagine the inverse agonist activity of R AM1241 at the rodent CB2 receptors, on the other hand Capecitabine Captabin to its agonist activity at the human receptor, results from various levels of CB2 constitutive activity between our rodent and human receptor appearance systems, giving rise to a case of protean agonism. Nevertheless, the observation that the human receptor shows higher basal activity compared to rat receptor reaches odds with this theory and indicates that other, up to now undefined, mechanisms might be involved.