Mitsuo Hayashida

Dose difference in β-adrenergic blockers with intrinsic sympathomimetic action to block β-adrenoceptors and induce sympathomimetic action

Abstract 1. 1. Isoprenaline, a β-adrenergic full agonist, and carteolol, befunolol and BFE-55, β-adrenergic blockers with an intrinsic sympathomimetic action, induced dose-related increases in heart rate when administered intravenously (i.v.). 2. 2. The β-partial agonists administered i.v. shifted a dose-heart rate increased response curve of isoprenaline, suggesting a competitive antagonism. 3. 3. In carteolol, doses to block β-adrenoceptors were found to be 400–1000 times lower than that to induce agonistic action. In BFE-55, doses to block β-adrenoceptors were equal to that to induce sympathomimetic action. The difference between doses of the befunolol to produce both actions was intermediate. 4. 4. These results suggest that there may be a difference between doses blocking β-adrenoceptors and inducing sympathomimetic action in some β-adrenergic partial agonists and, therefore, that there may exist β-partial agonists which do not induce sympathomimetic action in doses blocking β-adrenoceptors.

Effect of histamine on two different affinity sites in β-adrenoceptors

Abstract 1. 1. To study the effect of histamine on two different affinity sites in β-adrenoceptors, we tested specific binding of [ 3 H]befunolol to microsomal fractions from the guinea pig taenia caecum in the presence and absence of histamine (10 −5 M). 2. 2. The Scatchard plot of data in the absence of histamine was recognized as two straight lines suggesting the existence of two different affinity sites: high and low. However, a curvilinear plot with upward concavity was observed in the presence of histamine (10 −5 M). 3. 3. These results suggest the possibility that histamine alters the binding sites of β-adrenoceptors into several classes of sites with lower affinity. 4. 4. Further, an antagonism between isoprenaline and BFE-55, which interacts only with the high affinity site, was tested on the atria ( β 1 -adrenoceptor predominant) and tracheae ( β 2 -adrenoceptor predominant) of the guinea pig. The pA 2 -values in the atria were almost equal to those in the trachea, suggesting that both β 1 - and β 2 -adrenoceptors contained two different affinity sites.