Abstract

The beta adrenergic receptors of guinea-pig atria and trachea, previously classified as beta-1 and beta-2, respectively, were investigated in light of the hypothesis that similarity of isomeric activity ratios of adrenergic drugs in various tissues indicates similarity of the sites involved. Optical isomers of three agonists and three antagonists were selected for this purpose. The isomeric activity difference for (-)- and (+)-isoproterenol from atria is 3.0 log units (or 1000-fold) and that from trachea is 2.7 log units (or 500-fold). These values are not significantly different from one another. Similar analyses of isomeric activity differences for the optical isomers of norepinephrine and epinephrine reveal that differences in their isomeric ratios between the tissues are small. Orders of potencies of the agonists were markedly different in the two tissues. When measured at pA₁₀ levels, the isomeric activity differences, in log units, for (-)-and (+)-alprenolol, sotalol and 1-(4-nitrophenyl)-2-isopropylaminoethanol HCI from atria are 2.16, 1.68 and 2.0, respectively, and from trachea are 1.77, 1.84 and 2.31, respectively. Further analysis indicated that both (-)- and (+)-isomers of the beta blockers compete for the same site. Although the pA₂ values of (-)-sotalol varied as much as 1 log unit (or 10-fold) between atria and trachea, isomeric activity differences from both tissues are the same. The so-called "selective" beta adrenergic antagonist, (±)-practolol, was about 10 times more active on atria than on trachea. It thus appears that at least 10-fold variations in activity of agonists and antagonists can occur between tissues whereas isomeric activity differences display variations of only 2.5-fold. The data obtained from the optical isomers of agonists and antagonists suggest that beta adrenergic receptors in guinea-pig atria and trachea may be of a single type.