Fentanyl isothiocyanate reveals the existence of physically associated mu- and delta-opioid receptors mediating inhibition of adenylate cyclase in rat neostriatum.
Dopamine D-1 receptor-stimulated cyclic AMP efflux from superfused rat neostriatal slices was strongly inhibited by the delta-opioid receptor agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE, 1 microM), and by the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 1 microM). Naloxone (0.1 microM) fully antagonized the inhibitory effect of DAGO, leaving that of DPDPE virtually unchanged. Preincubation of the slices with the irreversible delta receptor ligand, fentanyl isothiocyanate (FIT, 1 microM) did not affect the inhibitory effect of DAGO, but prevented that of DPDPE. Naloxone no longer antagonized the inhibitory effect of DAGO when the delta receptors were selectively and irreversibly blocked by FIT. These data indicate that FIT and naloxone, acting on delta and mu receptors, respectively, may share a common binding site, suggesting the involvement of a functional mu, delta-opioid receptor-complex.
Schoffelmeer
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AN
Department of Pharmacology, Free University, Medical Faculty, Amsterdam, The Netherlands.
Rice
K C
KC
Heijna
M H
MH
Hogenboom
F
F
Mulder
A H
AH
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002421:Caudate Nucleus / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D017879:Isothiocyanates; D008297:Male; D011699:Putamen / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D000067956:Adenylyl Cyclase Inhibitors; D004745:Enkephalins; D017879:Isothiocyanates; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C037091:fentanyl isothiocyanate; D020881:Enkephalin, D-Penicillamine (2,5)-; D000242:Cyclic AMP; D005283:Fentanyl