IMIDAZOLINE RECEPTORS, NONADRENERGIC IDAZOXAN BINDING-SITES AND ALPHA(2)-ADRENOCEPTORS IN THE HUMAN CENTRAL-NERVOUS-SYSTEM

Both [H-3]clonidine and [H-3]idazoxan bind to alpha(2) adrenoceptors. The former also labels imidazoline receptors, and the latter non-adren ergic idazoxan binding sites. In order to investigate whether the imid azoline receptors and non-adrenergic idazoxan binding sites are identi cal, we compared the binding characteristics of[H-3]clonidine and [H-3 ]idazoxan to these sites by radioligand binding experiments on ultra-t hin slices and homogenates of human striatum. A good correlation was f ound between the effect of different ions on the binding characteristi cs of [H-3]clonidine and [H-3]idazoxan, and the affinities of most com peting drugs. However, clonidine and rilmenidine displayed a 100- and 10-fold lower affinity, respectively, for the idazoxan binding sites t han for the imidazoline receptors. Autoradiography with [H-3]clonidine showed that high densities of imidazoline receptors were present in t he striatum, pallidum, gyrus dentatus of the hippocampus, amygdala, an d substantia nigra. Moderate densities were found throughout the cereb ral cortex, thalamus and several brainstem nuclei including the nucleu s olivarius inferior. Low densities were seen in the cerebellum spinal cord and pituitary gland. As for the non-adrenergic sites labelled by [H-3]idazoxan, the imidazoline receptors can be found in all major br ain areas examined. However, there are some striking differences betwe en the concentrations of imidazoline receptors and non-adrenergic idaz oxan binding sites in certain brain regions. To reconcile distribution and pharmacologic data, we propose that imidazoline receptors and non -adrenergic idazoxan binding sites represent different proteins or pro tein complexes and that at least in the nucleus reticularis lateralis and the striatum, imidazoline receptors and non-adrenergic idazoxan bi nding sites may be physically associated. The regional distribution of alpha(2) adrenoceptors within the human CNS was determined by quantit ative autoradiography with [H-3]RX821002. The highest densities of alp ha(2) adrenoceptors were found in the cerebral and cerebellar cortex, and certain regions in the medulla oblongata (floor of the IV ventricl e, reticular formation, hypoglossal nucleus and nucleus olivarius infe rior). No alpha(2) adrenoceptors were detected in the pituitary gland. There exists no relationship between the distribution pattern of imid azoline receptors and alpha(2) adrenoceptors, indicating that these bi nding sites are independent from each other.