Short communication Effects of PB190 and PB212, new s receptor ligands, on glucocorticoid receptor-mediated gene transcription in LMCAT cells Gra¿yna Skuza 1 , Magdalena Szymañska 2 , Bogus³awa Budziszewska 2,3 , Carmen Abate 4 , Francesco Berardi 4 Department of Pharmacology, Department of Experimental Neuroendocrinology, Polish Academy of Sciences, Smêtna 12, PL 31-343 Kraków, Poland Department of Biochemical Toxicology, Chair of Toxicology, Jagiellonian University, Medical College, Medyczna 9, PL 30-688 Kraków, Poland Dipartimento Farmacochimico, Università degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy Correspondence: Gra¿yna Skuza, e-mail: skuza@if-pan.krakow.pl Abstract: The hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis is often observed in patients with major depression. It has even been implicated in the pathophysiology of this disease. Some antidepressant drugs (ADs) inhibit glucocorticoid receptor (GR) function under in vitro conditions. The s receptor agonists reveal potential antidepressant activity in animals, moreover, igmesine is promising as an AD in humans. As already shown, s receptors are involved in stress-induced responses (e.g., conditioned fear stress in mice). The aim of the present study was to find out whether the new selective s receptor ligands, PB190 and PB212, are able to af- fect directly the endocrine system activity. To this end, we evaluated their influence on GR function in mouse fibroblast cells (L929), stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) plasmid (LMCATcells). Fluvoxamine, a selective serotonin reuptake inhibitor, recognized as a s receptor agonist was used for comparison. The obtained re- sults showed that both PB190 and PB212 (potential s receptor agonist and antagonist, respectively) like fluvoxamine, decreased the corticosterone-induced CAT activity in a concentration-dependent manner. The significance of this fact remains ambiguous and re- quires further studies. Key words: selective s ligands, PB190, PB212, glucocorticoid-mediated gene transcription, fibroblast cells Introduction It has been demonstrated that several antidepressant drugs (ADs) have the affinity for s receptors in nano- molar range and that this fact may be relevant to their mechanism of antidepressant action [for review: 4, 8, 14, 24]. The s receptor ligands (especially s receptor agonists, e.g., igmesine, SA4503, (+)-pentazocine, UMB23 and UMB82) reveal potential antidepressant activity in animal models of depression, e.g., the forced swim test, tail suspension test, conditioned fear stress [17, 22, 29, 31]. Preclinical studies have shown that target- ing s receptors alone is sufficient (but not requisite) for production of antidepressant-like actions. More- 1564