Binding of endomorphin-2 to mu-opioid receptors in experimental mouse mammary adenocarcinoma.
Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) binds with high affinity and selectivity to the mu-opioid receptor. In the present study, [125I]endomorphin-2 has been used to characterize mu-opioid-binding sites on transplantable mouse mammary adenocarcinoma cells. Cold saturation experiments performed with [125I]endomorphin-2 (1 nM) show biphasic binding curves in Scatchard coordinates. One component represents high affinity and low capacity (K(d) = 18.79 +/- 1.13 nM, B(max) = 635 +/- 24 fmol/mg protein) and the other shows low affinity and higher capacity (K(d) = 7.67 +/- 0.81 microM, B(max) = 157 +/- 13 pmol/mg protein) binding sites. The rank order of agonists competing for the [125I]endomorphin-2 binding site was [d-1-Nal3]morphiceptin > endomorphin-2 >> [d-Phe3]morphiceptin > morphiceptin > [d-1-Nal3]endomorphin-2, indicating binding of these peptides to mu-opioid receptors. The uptake of 131I-labeled peptides administered intraperitoneally to tumor-bearing mice was also investigated. The highest accumulation in the tumor was observed for [d-1-Nal3)morphiceptin, which reached the value of 8.19 +/- 1.14% dose/g tissue.
Fichna
J
J
Department of Medicinal Chemistry, Medical University, Lodz, Poland.
do-Rego
J-C
JC
Mirowski
M
M
Costentin
J
J
Janecka
A
A
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D007457:Iodine Radioisotopes / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009842:Oligopeptides / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D007457:Iodine Radioisotopes; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105294:endomorphin 2