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 modulatio n of renal water handling, but whether their action is accomplished th rough central and/or peripheral mechanisms remains controversial. In d ifferent cell systems, on the other hand, opioids and somatostatin inh ibit cell proliferation. In the present study, we have used an establi shed cell line, derived from opossum kidney (OK) proximal tubules, in order to characterize opioid and somatostatin receptors and to investi gate the action of opioids and somatostatin on tubular epithelial tiss ue. Our results show the presence of one class of opioid binding sites with kappa(1) selectivity (K-D 4.6 +/- 0.9 nM, 57,250 sites/cell), wh ereas delta, mu, or other subtypes of the kappa site were absent. Soma tostatin presents also a high affinity site on these cells (K-D 24.5 n M, 330,000 sites/cell). No effect of either opioids or somatostatin on the activity of the Na+/P-i cotransporter was observed, indicating th at these agents do not affect ion transport mechanisms. However, opioi d agonists and somatostatin analogs decrease OK cell proliferation in a dose-dependent manner; in the same nanomolar concentration range, th ey displayed reversible specific binding for these agents. The additio n of diprenorphine, a general opioid antagonist, reversed the effects of opioids, with the exception of morphine. Furthermore, morphine inte racts with the somatostatin receptor in this cell line too, as was the case in the breast cancer T47D cell line. Our results indicate that i n the proximal tubule opioids and somatostatin do not affect ion trans port, but they might have a role in the modulation of renal cell proli feration either during ontogenesis or in kidney repair. (C) 1996 Wiley -Liss, Inc.