Identification and characterization of opioid and somatostatin binding sites in the opossum kidney (OK) cell line and their effect on growth.
Opioids and somatostatin analogs have been implicated in the modulation of renal water handling, but whether their action is accomplished through central and/or peripheral mechanisms remains controversial. In different cell systems, on the other hand, opioids and somatostatin inhibit cell proliferation. In the present study, we have used an established cell line, derived from opossum kidney (OK) proximal tubules, in order to characterize opioid and somatostatin receptors and to investigate the action of opioids and somatostatin on tubular epithelial tissue. Our results show the presence of one class of opioid binding sites with kappa, selectivity (KD 4.6 +/- 0.9 nM, 57,250 sites/cell), whereas delta, mu, or other subtypes of the kappa site were absent. Somatostatin presents also a high affinity site on these cells (KD 24.5 nM, 330,000 sites/cell). No effect of either opioids or somatostatin on the activity of the NA+/Pi cotransporter was observed, indicating that these agents do not affect ion transport mechanisms. However, opioid agonists and somatostatin analogs decrease OK cell proliferation in a dose-dependent manner; in the same nanomolar concentration range, they displayed reversible specific binding for these agents. The addition of diprenorphine, a general opioid antagonist, reversed the effects of opioids, with the exception of morphine. Furthermore, morphine interacts with the somatostatin receptor in this cell line too, as was the case in the breast cancer T47D cell line. Our results indicate that in the proximal tubule opioids and somatostatin do not affect transport, but they might have a role in the modulation of renal cell proliferation either during ontogenesis or in kidney repair.
Hatzoglou
A
A
Laboratory of Experimental Endocrinology, University of Crete, School of Medicine and University Hospital, Heraklion, Greece.
Bakogeorgou
E
E
Papakonstanti
E
E
Stournaras
C
C
Emmanouel
D S
DS
Castanas
E
E
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001693:Biological Transport, Active; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004174:Diprenorphine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007477:Ions; D007668:Kidney / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000819:agonists / Q000494:pharmacology; D009893:Opossums; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000737:chemistry* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000737:chemistry* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000737:chemistry* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D007477:Ions; D009294:Narcotics; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D017481:Receptors, Somatostatin; D004174:Diprenorphine; D013004:Somatostatin; D009020:Morphine; D012964:Sodium