title: The kappa-opiate agonist U50488H decreases the entry of 45Ca into rat cortical synaptosomes by inhibiting N- but not L-type calcium channels.
abstract: The selective kappa-opiate agonist U50488H (1-100 microM) significantly reduced the uptake of 45Ca into cortical synaptosomes from the brain of the rat, in a time- and dose-dependent manner. In physiological medium, the maximum inhibition occurred after 2 min; this was approximately 55% (at 100 microM) and the IC50 was 80 nM. Nifedipine (1 microM) had no significant effect on the influx of Ca2+ in physiological medium (containing 5 mM K+), though, in fact, there was an approximately 20% decrease in the presence of 100 microM of drug. Nifedipine, however, did cause a significant blockade of the entry of 45Ca in medium containing 10 or 15 mM K+, demonstrating that L-type channels on synaptosomes were operational under depolarising conditions. Under these depolarising conditions, there was an additive inhibitory effect on entry of 45Ca into synaptosomes when U50488H (1 microM) and nifedipine (1 microM) were incubated together. Treatment of synaptosomes with omega-conotoxin (omega-CgTx, 0.5 microM) resulted in a 35% reduction in the uptake of 45Ca. omega-Conotoxin (0.5 microM) or naloxone (20 microM) abolished the inhibitory effect of U50488H on the uptake of 45Ca, but naloxone did not alter the blockade of L-type Ca2+ channels, caused by nifedipine. In conclusion, the data demonstrate that under depolarising conditions, there are functional L-type calcium channels on nerve endings in the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, London, U.K.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Xiang
authors.forename: P
authors.initials: P
authors.lastname: Adamson
authors.forename: M J
authors.initials: MJ
authors.lastname: Brammer
authors.forename: I C
authors.initials: IC
authors.lastname: Campbell
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D009467:Neuromuscular Depolarizing Agents; D010456:Peptides, Cyclic; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020866:omega-Conotoxin GVIA; D007770:L-Lactate Dehydrogenase; D009543:Nifedipine; D011188:Potassium; D002118:Calcium