The effect of kappa agonist U50-488H on [3H]nimodipine receptor binding in rat brain regions

The effects of a kappa opiate agonist have been evaluated on [3H]nimodipine binding to dihydropyridine receptors for 'L'-type Ca2+ channels in rat brain regions. Administration of U50-488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1,-pyrolidinyl-cyclohexyl benzeneacetamide) produced a 28% decrease in Bmax in cortex and a 23% decrease in cerebellum. No changes were seen in the affinity (Kd) for [3H]nimodipine binding sites. Slight changes in hippocampal and striatal binding capacities were observed with no changes seen in hypothalamus and brainstem. The kappa antagonist MR2266 effectively reversed in vivo all changes in [3H]nimodipine binding without producing any effect alone. These studies suggest that kappa opiate receptors may be directly coupled to L-type calcium channels as evidenced by [3H]nimodipine binding studies and may account for the findings that kappa opiate agonists inhibit neurotransmitter release by allosterically interfering with the Ca2+ channel protein in brain membranes.