Effect of histamine on two different affinity sites in beta-adrenoceptors.

1. To study the effect of histamine on two different affinity sites in beta-adrenoceptors, we tested specific binding of [3H]befunolol to microsomal fractions from the guinea pig taenia caecum in the presence and absence of histamine (10(-5) M). 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. These results suggest the possibility that histamine alters the binding sites of beta-adrenoceptors into several classes of sites with lower affinity. 4. Further, an antagonism between isoprenaline and BFE-55, which interacts only with the high affinity site, was tested on the atria (beta 1-adrenoceptor predominant) and tracheae (beta 2-adrenoceptor predominant) of the guinea pig. The pA2-values in the atria were almost equal to those in the trachea, suggesting that both beta 1- and beta 2-adrenoceptors contained two different affinity sites.