A given overall level of beta-adrenergic receptor occupancy by agonist can involve either high or low turnover of occupancy with respect to individual receptors, depending on the binding properties of the particular agonist. It was recently demonstrated that, for epinephrine-stimulated adenylate cyclase activation in the S49 cell, a portion of the separation between the beta-adrenergic receptor binding curve and the cyclase response curves is dependent on high occupancy turnover (high binding frequency). By involving a larger number of receptors within a short period of time than are bound at any one instant, the effect of high binding frequency is to increase the rate of GTP-binding protein/adenylate cyclase activation over the rate that is observed when the mobility of the number of receptors occupied at any given instant is the rate-limiting factor. This phenomenon contributes to the normal dose-response curve for epinephrine, according to our analysis, but only in combination with the apparent high efficiency of the receptor in the epinephrine-bound state at cyclase activation. Here we examined the potential combination of the contributions of agonist binding frequency and intrinsic efficiency to the adenylate cyclase activation rate for four other beta-adrenergic agonists (isoproterenol, zinterol, metaproterenol, and dobutamine). This was done by a comparison of the response (1-min cAMP accumulation) between a point on the normal dose versus response curve (control) with the response under conditions in which the concentration of agonist-bound receptors was identical to control but the absolute number of receptors involved in maintaining that concentration was significantly reduced. In the experiments, the majority of the receptors were blocked by the beta-adrenergic antagonist propranolol, which has a relatively long occupancy half-life. The remaining receptors were occupied by agonist such that the concentration of bound receptors was identical to the control condition of low occupancy of the full complement of receptors in the absence of antagonist. Compared with control, the experimental condition was one in which agonist occupancy turnover was inhibited and the potential contribution of agonist binding frequency as a factor contributing to the cyclase activation rate was greatly reduced (producing a point on the receptor mobility-limited dose versus response curve). Isoproterenol and metaproterenol show evidence that their binding frequencies and the efficiency of the receptor when bound to them are of such a combination that the normal dose-response curves for these agonists contain a component that is dependent on the binding frequency.(ABSTRACT TRUNCATED AT 400 WORDS)