Abstract

It has been suggested that 5-hydroxytryptamine (serotonin)-containing neurons influence the regulation of central beta adrenoceptors caused by antidepressants. [3H]Dihydroalprenolol ( [3H] DHA) was the radioligand used in these previous studies to measure beta adrenoceptors. In this study, we compared the binding characteristics of [3H]DHA with those of [125I]iodopindolol ( [125I]PIN) and used [125I]IPIN to study effects of lesioning serotonergic nerves on the regulation of beta adrenoceptors. A comparison was made in homogenates prepared from rat frontal cortex of the specific binding of [3H]DHA with that of [125I]IPIN to beta adrenoceptors. Nonlinear regression analysis of saturation experiments of [3H]DHA binding to cortical homogenates indicated that a two-component binding model fit the data significantly better than a one-component model. A dissociation constant value of 0.47 +/- 0.16 nM and a Bmax value of 62 +/- 7 fmol/mg protein were obtained for the high-affinity site. The low-affinity site was poorly defined. Rosenthal transformations of the saturation isotherms for [3H]DHA binding were clearly curvilinear. By contrast, nonlinear regression analysis of saturation experiments of the binding of [125I]IPIN indicated that the binding of this radioligand was described adequately by a one-component model and yielded a dissociation constant value of 147 +/- 10 pM with a Bmax of 80 +/- 5 fmol/mg protein. Rosenthal transformations of the [125I]IPIN data were linear. From such data, it was inferred that [3H]DHA binds to some site in addition to beta adrenoceptors, whereas [125I]IPIN does not.(ABSTRACT TRUNCATED AT 250 WORDS)