Distribution of beta‐adrenergic receptor subtypes in human post‐mortem brain: Alterations in limbic regions of schizophrenics

The distribution of the beta₁ (β₁) and beta₂ (β₂) subtypes of the β‐adrenergic receptor was examined in rat and nondiseased control human tissue. The distribution of the β₁ and β₂ receptors was also examined in schizophrenic cases, with additional studies in schizophrenic suicide and nonschizophrenic suicide cases. Scatchard analysis of the binding of [¹²⁵I]iodopindolol (IPIN) to cortical membranes showed a similar K_d in human (177 pM) and rat (161 pM), but a lower maximum binding site (B_max) in the human tissue (18.7 fmol/mg protein and 55.6 fmol/mg protein). For the autoradiographic studies [¹²⁵I]IPIN was used to visualize both subtypes (total) or was displaced with the selective β₁‐receptor antagonist ICI‐89,406 to visualize β₂ sites, or with the selective β₂‐receptor antagonist ICI‐118,551 to visualize β₁ sites. Important differences in the regional distribution of the two subtypes of the β‐adrenergic receptors were noted between rat and human. In the nucleus accumbens and ventral putamen (ventral striatum), a patchy distribution of β₁ receptors was observed that was not evident in the rat. These patches were aligned with markers of the matrix compartment of the striatum. The schizophrenic cases showed significant increases in the labeling of the β₁‐receptor patches with [¹²⁵I]IPIN. In contrast to the frontal cortex of the nondisease controls, the parietal and temporal cortex showed a high ratio of β₁ to β₂ receptors and a highly laminar organization of the subtypes. [¹²⁵I]IPIN binding to β₁ receptors was highest in the external laminae with the reverse gradient for the β₂ subtype. The medial temporal cortex displayed an alteration in the ratio of the 2 subtypes of the β‐adrenergic receptor, with the parahippocampus and hippocampus of the human, in contrast to the rat brain, predominantly expressing the β₂ receptor. Moreover, there were consistently higher densities of β₂ receptors in the hippocampus of the right hemisphere than the left hemisphere of the nondisease controls. There was not a left and right hemispheric asymmetry of β₂ receptors in the hippocampus of elderly schizophrenics or in young schizophrenics who committed suicide. The asymmetry was evident in nonschizophrenic suicides, suggesting that the lack of asymmetry in the hippocampus of schizophrenics is evident early in the disease process. Thus limbic structures show alterations in the patterning of β₁ and β₂ receptors in the schizophrenic cases.