Inhibition experiments of (−)[3H]CGP 12177 binding by (−)isoproterenol and salbutamol were performed on synaptosomes prepared from rat brain cortex and cerebellum. Adenylyl cyclase (AC) stimulation experiments on slices of these structures were also performed, with measuring [14C]cAMP obtained from [14C]adenine. Studyingβ1- andβ2-adrenoceptors (β2AR) separately, dissociation constants of (−)isoproterenol for the high- (KH) and low- (KL) affinity states are 8 and 206nM, respectively, forβ1AR,vs20 and 900nMforβ2AR. With salbutamol, KHand KLforβ2AR are 37 and 1250nM, respectively,vs430 and 8500nMforβ1AR. In any case, the proportion of high-affinity state (RH) ofβ2AR in the cerebellum (59% and 35% for (−)isoproterenol and salbutamol, respectively) is twice that ofβ1AR (30% and 18%). Surprisingly, the RHof cortexβ2AR with (−)isoproterenol (30%) is significantly lower than in the cerebellum, but not with salbutamol (35%).To allow meaningful comparisons of potencies in stimulating [14C]cAMP production, we define the coupling efficiency (CE), applicable to specifiedβAR subtype and agonist, and expressed as the maximal production of molcAMP.mol−1βAR.min−1. The order of CE was always in favor of (−)isoproterenolvssalbutamol on cerebellumβ2AR>on cortexβ2AR>on cortexβ1AR. This order indicates the partial agonism of salbutamol for bothβAR subtypes, and an intrinsic better coupling ofβ2ARvsβ1AR in rat brain. Moreover, this order corresponds roughly to that of RH. Hence, CE is directly correlated with RHat least for these two agonists. EC50for cAMP production for each subtype and agonist is in the same order than the respective KL, and might only reflect the rapid return of receptor to low-affinity state after the activation of Gsprotein.In binding experiments on the wholeβAR in both areas, the pseudo-Hill coefficient did not reach 1 with 0.3mMguanosine 5′-(β,gg-imido)triphosphate (GppNHp). This dysfunction of GppNHp in rat brain structures might be caused by a major difference in the regulation of coupling in the ternary complex as compared with peripheral tissues.