Different subtypes of opioid receptors have different affinities for G-proteins.
In this work, we have characterized the opioid receptor expressed by the human neuroblastoma cell line SK-N-BE and compared its hydrodynamic behaviour with those of well known opioid receptors: mu-opioid receptor of rabbit cerebellum and delta-opioid receptor of the hybrid cell line NG 108-15. Human neuroblastoma cell line SK-N-BE expresses a substantial amount of opioid receptors (200-300 fmoles/mg of protein). Pharmacological characterization suggests an heterogenous population of receptors and the presence of two delta subtypes which are, at least partially, negatively coupled with adenylate cyclase via a Gi protein. These receptors exist under two different molecular forms and, in this respect, strikingly contrast with the archetypic delta receptors of NG 108-15 hybrid cell line which show only a high molecular weight form and appear more tightly coupled with the G protein. Hydrodynamic behaviour of SK-N-BE opioid receptors is reminiscent of the profile observed with the rabbit cerebellum mu-opioid receptor. This observation is consistent with the presence of two delta-opioid receptors subtypes, one of which exhibiting properties close to those of mu opioid receptors. Taken overall, our results suggest that different types and subtypes of opioid receptors, even if they are coupled to the same inhibitory G protein, are more or less tightly coupled with their transduction proteins and that closely related opioid receptors can form allosterically interacting complexes.
Polastron
J
J
Laboratoire de Neurosciences, CNRS URA 1829, Caen, France.
Jauzac
P
P
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002531:Cerebellum / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004174:Diprenorphine / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000145:classification* / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000145:classification / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004745:Enkephalins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C059567:deltorphin; D004174:Diprenorphine; D005576:Colforsin; D009270:Naloxone; D005048:Etorphine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C037653:deltakephalin; D020881:Enkephalin, D-Penicillamine (2,5)-; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases