Apparent affinity values of beta-adrenergic blockers in a tissue with a mixture of beta-adrenergic receptor subtypes.
The affinity (pA2 or pKB) values of 3 different beta-adrenoceptor blocking drugs were determined using the isolated guinea-pig tracheal chain preparation. The pA2 values for each of the beta-adrenoceptor blocking drugs were determined, using respectively isoprenaline and salbutamol as agonists. Neuronal and extraneuronal uptake of agonist were blocked with phenoxybenzamine. With isoprenaline, a nonselective beta-adrenoceptor agonist, the pA2 values for the blocking drugs were unacceptable. Using the beta 2-selective beta-adrenoceptor agonist, salbutamol, under the same conditions, resulted in consistent pA2 values for the nonselective beta-adrenoceptor blocking drug propranolol and some concentrations of the beta 2-selective blocking drug ICI 118.551. pA2 Values for the beta1-selective antagonist atenolol were not consistent for the concentrations used. It is suggested that this is due to the guinea-pig trachea having a mixed beta-adrenoceptor population. A mathematical model is presented that shows the influence of a mixed receptor subpopulation on the shift of theoretical agonist concentration-effect curves in the presence of a competitive antagonist. It can be shown that the affinity values of antagonists for a specific receptor subtype are to a greater or lesser degree unreliable, depending upon the selectivity-ratios of both the agonist and the antagonist used.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000037:antagonists & inhibitors; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000294:innervation
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D000420:Albuterol