DISTRIBUTION OF BETA-ADRENERGIC-RECEPTOR SUBTYPES IN HUMAN POSTMORTEM BRAIN - ALTERATIONS IN LIMBIC REGIONS OF SCHIZOPHRENICS

The distribution of the beta-1 (beta-1) beta-2 (beta-2) subtypes of the beta-adrenergic receptor was examined in rat and nondiseased control human tissue. The distribution of the beta-1 and beta-2 receptors was also examined in schizophrenic cases, with additional studies in schizophrenic suicide and nonschizophrenic suicide cases. Scatchard analysis of the binding of [I-125]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 [I-125]IPIN was used to visualize both subtypes (total) or was displaced with the selective beta-1-receptor antagonist ICI-89,406 to visualize beta-2 sites, or with the selective beta-2-receptor antagonist ICI-118,551 to visualize beta-1, sites. Important differences in the regional distribution of the two subtypes of the beta-adrenergic receptors were noted between rat and human. In the nucleus accumbens and ventral putamen (ventral striatum), a patchy distribution of beta-1, 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 beta-1-receptor patches with [I-125]IPIN. In contrast to the frontal cortex of the nondisease controls, the parietal and temporal cortex showed a high ratio of beta-1 to beta-2 receptors and a highly laminar organization of the subtypes. [I-125]IPIN binding to beta-1 receptors was highest in the external laminae with the reverse gradient for the beta-2 subtype. The medial temporal cortex displayed an alteration in the ratio of the 2 subtypes of the beta-adrenergic receptor, with the parahippocampus and hippocampus of the human, in contrast to the rat brain, predominantly expressing the beta-2 receptor. Moreover, there were consistently higher densities of beta-2 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 beta-2 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 beta-1 and beta-2 receptors in the schizophrenic cases.