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[Cancer Research 55, 5632-5636, December 1, 1995]
© 1995 American Association for Cancer Research

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Morphine Cross-Reacts with Somatostatin Receptor SSTR2 in the T47D Human Breast Cancer Cell Line and Decreases Cell Growth1

Anastassia Hatzoglou2, L'Houcine Ouafik, Efstathia Bakogeorgou, Kyriaki Thermos and Elias Castanas

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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Copyright © 1995 by the American Association for Cancer Research.