title: Capsaicin inhibits the in vitro binding of peptides selective for mu- and kappa-opioid, and nociceptin-receptors.
abstract: Capsaicin inhibited the equilibrium specific binding of endogenous opioid-like peptide ligands such as endomorphin-1, nociceptin, and dynorphin((1-17)) in rat brain membrane preparations. We studied the in vitro effect of capsaicin (1-10 microM) on homologous and heterologous competitive binding of opioid ligands, using unlabeled synthetic peptides and the following tritiated compounds: [(3)H]endomorphin-1, [(3)H]endomorphin-2, [(3)H]nociceptin((1-17)) and [(3)H]dynorphin((1-17)). Capsaicin-dependent inhibition was also observed in [(35)S]GTPgammaS stimulation assays in the presence of certain opioid peptides. The inhibition of opioid binding was further investigated using other synthetic and natural mu-opioid ligands such as [D-Ala(2),(NMe)Phe(4),Gly(5)-ol]enkephalin (DAMGO), morphine and naloxone. The decrease in opioid ligand affinity upon capsaicin treatments was most apparent with endomorphin-1, followed by nociceptin and dynorphin. The binding of other investigated opioids were not affected in the presence of capsaicin. In [(3)H]endomorphin-1 binding assays, capsazepine antagonized the inhibitory effect of capsaicin in rat brain membranes suggesting the involvement of TRPV1 receptors. In Chinese hamster ovary (CHO) cells stably expressing mu-opioid receptors, but lacking vanilloid receptors, the inhibition by capsaicin on the binding of [(3)H]endomorphin-1 was not present. It is concluded that the inhibitory effect of capsaicin on the receptor binding affinity of endogenous opioid peptides in brain membrane preparations seems not to be a direct effect, it is rather a negative feedback interaction with opioid receptors.
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, H-6726 Szeged, Temesvari krt. 26, Hungary. wolleman@brc.hu
authors.forename: Mária
authors.initials: M
authors.lastname: Wollemann
authors.forename: Eniko
authors.initials: E
authors.lastname: Ioja
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
mesh_terms: D000701:Analgesics, Opioid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D016466:CHO Cells; D002211:Capsaicin / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004399:Dynorphins / Q000737:chemistry / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D018847:Opioid Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D018689:Sensory System Agents / Q000378:metabolism*; D014316:Tritium / Q000737:chemistry; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000701:Analgesics, Opioid; D002211:Capsaicin; D004399:Dynorphins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D008024:Ligands; D009842:Oligopeptides; D018847:Opioid Peptides; D010455:Peptides; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D018689:Sensory System Agents; D014316:Tritium; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C105293:endomorphin 1