Biochemical evidence of functional interaction between mu- and delta-opioid receptors in SK-N-BE neuroblastoma cell line.
Radioligand binding assays and functional experiments revealed that the SK-N-BE neuroblastoma cell line expresses a similar ratio of mu- and delta-opioid receptors, both negatively coupled to adenylyl cyclase through pertussis toxin-sensitive G proteins. Our findings also indicate that some functional interaction occurred between the two opioid subtypes; in fact, long-term exposure to [D-Ala2-N-methyl-Phe4-Gly-ol5]enkephalin (DAMGO), a mu-selective agonist, sensitized the functional response of the delta-selective agonist but not vice versa. It is interesting that in acute interaction experiments, we observed a shift to the right of the concentration-effect curve of either DAMGO or [D-Pen2,5]enkephalin (DPDPE), a delta-selective agonist, as a result of DPDPE or DAMGO administration, respectively. In addition, low doses of naloxone, an antagonist selective for mu receptors, increased the inhibitory effect [D-Ala2-D-Met5]enkephalinamide (DAME), a mixed mu/delta agonist, on adenylyl cyclase activity. Taken overall, these data support the hypothesis of the existence of a cross talk between mu and delta receptors in the SK-N-BE cell line.
Palazzi
E
E
Department of Medical Pharmacology "Emilio Trabucchi," University of Milano, Milano, Italy.
Ceppi
E
E
Guglielmetti
F
F
Catozzi
L
L
Amoroso
D
D
Groppetti
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects; D009447:Neuroblastoma; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology
D000700:Analgesics; D004745:Enkephalins; D008565:Membrane Proteins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D000262:Adenylyl Cyclases