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Laboratories of Experimental Endocrinology [A. H., E. B., E. C.] and Pharmacology [K. T.], University of Crete, School of Medicine, and University Hospital, P.O. Box 1393, Heraklion GR-71110, Crete, Greece, and Laboratoire de Cancerologie Experimentale, CJF INSERM 93-11 [A. H., E. C.], and Neuroendocrinologie Experimentale, U 297 INSERM [L. O.], Faculté de Medecine Nord, Marseille, France
In a previous study, we found that morphine decreases, in a dose-dependent manner, the cell growth of T47D human breast cancer cells, despite the lack of µ opioid receptors and an interaction of morphine with other opioid sites. We have therefore examined a possible interaction of morphine with other membrane receptor systems of the cell. The present study describes for the first time an interaction between µ-acting opioid drugs and the somatostatinergic system. We have found that [125I]Tyr11-somatostatin binds with high affinity to T47D cells. Analysis of the binding data showed the presence of two components: one with high affinity but low capacity (Kd, 0.145 nM; 1450 sites/cell), and another of lower affinity but higher capacity (Kd,1.192 nM; 11920 sites/cell). Somatostatin-14 and somatostatin-28 showed multiphasic displacement curves, indicating heterogeneity of binding sites. The latter was confirmed by reverse transcription-PCR, which revealed the existence of the somatostatin receptor subtypes 2 and 3 (SSTR2 and SSTR3), with a relative mRNA concentration of 85 and 15%, respectively. Morphine and the morphinomimetic peptide morphiceptine (Tyr-Pro-Phe-Pro-NH2) displace somatostatin from its binding sites. Further analysis indicated that µ-acting opioids interact with the SSTR2 receptor subtype.
1 This work was partially supported by the University of Crete Research Committee, Ministry of Health (KESY), and Hellenic Anticancer Society grants.
2 To whom requests for reprints should be addressed.
Received 5/ 2/95. Accepted 8/31/95.
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