title: Inhibitory effects of NaCl and guanyl-5'yl-imidodiphosphate (GppNHp) on [3H]naloxone binding to kappa-opioid receptors in guinea pig cerebellum.
abstract: Studies were performed to characterize the opioid receptors in guinea pig brain using the radiolabeled opioid antagonists, [3H]naloxone and [3H]diprenorphine and the kappa-agonist [3H]U-69593. The binding of [3H]U-69593 to guinea pig cerebellar membranes was reduced by NaCl, guanyl-5'yl-imidodiphosphate (GppNHp) and NaCl+GppNHp, and [3H]naloxone binding to cerebellar membranes was also reduced by NaCl and GppNHp. In the guinea pig cerebral cortex and striatum and the rat cerebellum, [3H]naloxone binding was not affected significantly by GppNHp in the presence or absence of 100 nM [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) and [D-Ala2, D-Leu5]enkephalin (DADLE). Guinea pig cerebellar [3H]diprenorphine binding was not affected by NaCl, GppNHp or NaCl+GppNHp. Furthermore, [3H]naloxone binding was reduced after pretreating cerebellar membranes with N-ethylmaleimide (NEM), which also attenuated GppNHp-induced inhibition of cerebellar [3H]naloxone binding. These results suggest that the properties of [3H]naloxone binding in guinea pig cerebellum differ from those in other brain regions and rat cerebellum, and that the interaction of [3H]naloxone and [3H]U-69593, but not [3H]diprenorphine, with guinea pig cerebellar opioid receptors is associated with a G-protein.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nihon University, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ishige
authors.forename: M
authors.initials: M
authors.lastname: Makimura
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Murakoshi
mesh_terms: D000818:Animals; D044482:Benzeneacetamides; D001665:Binding Sites; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004174:Diprenorphine / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009270:Naloxone / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004174:Diprenorphine; D006165:Guanylyl Imidodiphosphate; D009270:Naloxone; D012965:Sodium Chloride; D016308:Enkephalin, Leucine-2-Alanine; C045444:U 69593; D005033:Ethylmaleimide