Effect of S(-)- and R(+)-salsolinol on the POMC gene expression and ACTH release of an anterior pituitary cell line.
Tetrahydroisoquinolines (TIQs) are thought to play an important role in the process of development of alcohol dependence. Being a condensation product between the alcohol metabolite acetaldehyde and dopamine they might be involved in the balance of the opioid system as well as the reward system. Therefore, the influence of the TIQ salsolinol (SAL) on the pro-opiomelanocortin (POMC) gene expression was investigated using the ArT-20 mouse anterior pituitary tumor cell line. Our results show a significant decrease in the POMC gene expression by the S(-)-enantiomer of SAL. The basal secretion of adrenocorticotropin (ACTH) as well as the corticotropin-releasing factor (CRF)-stimulated ACTH released remained unchanged after R(+)- and S(-)-SAL treatment. Interestingly, it was clearly shown that a reduction of intracellular cAMP level occurred after the treatment of the cells with S(-)-SAL whereas R(+)-SAL did not affect the cAMP production. The obtained results suggest that S(-)-SAL is possibly involved in the establishment of the opioid deficiency in alcoholics.
Research Institute for Molecular Pharmacology, Department of Cellular & Biochemical Pharmacology, Berlin, Germany.
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I
Putscher
H
H
Haber
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A
Winkler
J
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Fickel
M F
MF
Melzig
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D007546:Isoquinolines; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C036617:salsolinol; D000242:Cyclic AMP