Characterization of kappa(1)-opioid receptor binding in human insular cortex

Mesolimbic dopaminergic neurotransmission is modulated by dynorphin peptide s binding to kappa-opioid receptors. The interaction between dynorphin and dopamine systems makes the kappa-opioid receptor a potential drug discovery target for the development of therapeutic agents for schizophrenia and dru g abuse. This study reports the specificity and parameters of [H-3]U69593 b inding in the insular cortex, a representative corticolimbic area of the hu man brain. The results demonstrate that the radioligand [H-3]U69593 labels a single population of receptors in human insular cortex with an affinity i n the low nanomolar range. The pharmacological profile for inhibition of [H -3]U69593 binding was determined in this brain region using drugs known to bind to mu, kappa and delta opioid receptors. The results show that kappa-o pioid selective agonists and antagonists inhibit binding of this ligand in human brain with comparable affinities and rank order as previously describ ed for rat and guinea pig brain and the cloned kappa(1)-opioid receptor sub type.