Relative efficacy of prenalterol and pirbuterol for beta-1 adrenoceptors: measurement of agonist affinity by alteration of receptor number.

Both prenalterol and pirbuterol are partial agonists (when compared to isoproterenol) in rat left atria. Schild analysis with the beta-1 adrenoceptor selective antagonist atenolol indicated that all three agonists stimulate beta-1 adrenoceptors in this preparation. Atria from rats implanted with mini-osmotic pumps which delivered isoproterenol (400 micrograms kg-1 hr-1) s.c. for 4 days were 9 times less sensitive than control, to isoproterenol, and produced no responses to either prenalterol or pirbuterol. Schild analysis with atenolol on these desensitized atria indicated a homogeneous population of beta-1 adrenoceptors. In the desensitized atria, both prenalterol and pirbuterol functioned as competitive antagonists of responses to isoproterenol and Schild analysis yielded estimates of the equilibrium dissociation constants (Kp) of prenalterol (0.09 micron) and pirbuterol (2 micron) in these tissues. The estimates of Kp were utilized to calculate the relative efficacy of pirbuterol and prenalterol; pirbuterol was shown to have 2.3 times the efficacy of prenalterol on beta-1 adrenoceptors. The implications of this method as a means of calculating the Kp for partial agonists are discussed. These data also serve as a caveat to the use of pirbuterol in the determination of functional cardiac beta adrenoceptor subtypes in experimental animals and in man.