The effects of dynorphin A (1-13) and U50, 488H on free intracellular calcium in guinea pig cerebellar synaptosomes.
The effects of the kappa-selective ligands dynorphin A (1-13) (DYN) and U50, 488H (U50) on free intracellular calcium were evaluated using synaptosomes prepared from the cerebellum of the guinea pig, an area with a high density of kappa receptors. DYN (10 microM) produced small nonsignificant decreases in basal free intracellular calcium (5-7%). U50 (10 microM) produced significant 15-20% decreases in basal free intracellular calcium which were reversed by nor-BNI (1 microM). When intracellular calcium levels were increased 8-10% by the administration of c-AMP or forskolin, DYN (10 microM) produced significant decreases in intracellular calcium of 10%. The effects of U50, 488H were not enhanced by increasing the synaptosomal levels of c-AMP. Neither DYN nor U50 (1 microM) significantly blocked the rise in free intracellular calcium induced by 50 mM KCI. When intracellular calcium concentrations were increased by the administration of 50 mM KCI prior to the administration of DYN or U50 (10 microM), the kappa ligands decreased intracellular calcium concentrations. These data indicate that DYN and U50 interact with kappa receptors resulting in a decrease in free intracellular calcium possibly via an enhancement of the efflux of calcium. The modulation of intracellular free calcium by the kappa opioids may be a mechanism by which these opioids produce their biological effects.
Olson
K G
KG
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Welch
S P
SP
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D004399:Dynorphins / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D010446:Peptide Fragments / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017473:Receptors, Opioid, kappa; D012016:Reference Values; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000700:Analgesics; D010446:Peptide Fragments; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins; D002118:Calcium