[3H]dynorphin a binding and [kappa] selectivity of prodynorphin peptides in rat, guinea-pig and monkey brain

Abstract

We have previously demonstrated that [3H]dynorphin A selectively labels [kappa] opioid receptors in guinea-pig whole brain. In these current studies, using protection from inactivation by [beta]-chloronaltrexamine ([beta]-CNA), we are able to demonstrate that although dynorphin A prefers [kappa] receptors, it will label [mu] receptors when [kappa] receptors are not available, or present in only a small number. Thus, differences in numbers of [mu] and [kappa] receptors present in brain preparations are critical in determining the receptor binding profile of [3H]dynorphin A across species. Additionally, lthough all the prodynorphin derived peptides show [kappa] preference, the ability of the other prodynorphin derived peptides to compete with [3H]dynorphin A for its receptor varies across species. Consequently, in a highly enriched [kappa] preparation such as monkey cerebral cortex, [3H]dynorphin A appears to label [kappa] receptors with substantial selectivity, and the other prodynorphin-derived peptides show less ability to compete with dynorphin A for its receptor. In contrast, in a [kappa]-poor tissue such as rat brain, all of the prodynorphin-derived peptides, including dynorphin A-(1-8), show very similar potency. Thus, differences in [mu] and [kappa] receptor numbers across brain regions and species lead to differences in the receptor binding profile of dynorphin A.