A novel kappa agonist inhibits [3H]nimodipine binding to a Ca++ channel receptor protein in rat brain.
The novel kappa agonist U50-488H in vitro produced a concentration-dependent decrease (0.25-25 microM) in [3H]nimodipine binding in neuronal P2 fractions [corrected] from rat brain cortex. Kinetic analysis indicates the decrease in binding results from a reduced Bmax with no change in affinity (Kd). The kappa antagonist, MR2266, blocked the decrease in [3H]nimodipine binding to membrane fractions. At equimolar concentrations (25 microM), morphine in vitro had no effect on [3H]nimodipine binding, while U50-488H demonstrated potent inhibition. Further kinetic analysis indicates that the IC50 for U50-488H is 0.5-0.7 microM with a KI by a Dixon plot of 1.5-1.7 microM [corrected]. These results suggest that kappa opiate receptors may be coupled to dihydropyridine receptors and as a result modulate Ca++ entry and neurotransmitter release in brain neurons.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001575:Benzomorphans / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D001923:Brain Chemistry; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology; D009553:Nimodipine / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa
D001575:Benzomorphans; D007473:Ion Channels; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C027247:MR 2266; D009553:Nimodipine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine