1 The aim of this study was to investigate the mechanism by which amphetamine exerts its inhibitory e ect on testicular interstitial cells of male rats. 2 Administration of amphetamine (10 712 ± 10 76 M) in vitro resulted in a dose-dependent inhibition of both basal and human chorionic gonadotropin (hCG, 0.05 iu ml 71 )-stimulated release of testosterone. 3 Amphetamine (10 79 M) enhanced the basal and hCG-increased levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in vitro (P50.05) in rat testicular interstitial cells. 4 Administration of SQ22536, an adenylyl cyclase inhibitor, decreased the basal release (P50.05) of testosterone in vitro and abolished the inhibitory e ect of amphetamine. 5 Nifedipine (10 76 M) alone decreased the secretion of testosterone (P50.01) but it failed to modify the inhibitory action of amphetamine (10 710 ± 10 76 M). 6 Amphetamine (10 710 ± 10 76 M) signi®cantly (P50.05 or P50.01) decreased the activities of 3b-hydroxysteroid dehydrogenase (3b-HSD), P450c17, and 17-ketosteroid reductase (17-KSR) as indicated by thin-layer chromatography (t.l.c.). 7 These results suggest that increased cyclic AMP production, decreased Ca 2+ channel activity and decreased activities of 3b-HSD, P450c17, and 17-KSR are involved in the inhibition of testosterone production induced by the administration of amphetamine.

Endocrine sensitivity, assessed by the expression of estrogen receptor (ER), has long been the predict factor to guide therapeutic decisions. Tamoxifen has been the most successful hormonal treatment in endocrine-sensitive breast cancer. However, in estrogen-insensitive cancer tamoxifen showed less effectiveness than in estrogen-sensitive cancer. It is interesting to develop new drugs against both hormone-sensitive and insensitive tumor. In this present study we examined anticancer effects of evodiamine extracted from the Chinese herb, Evodiae fructus, in estrogen-dependent and –independent human breast cancer cells, MCF-7 and MDA-MB-231 cells, respectively. Evodiamine inhibited the proliferation of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with concentration of 1×10−6 and 1×10−5 M. Evodiamine also induced apoptosis via up-regulation of caspase 7 activation, PARP cleavage (Bik and Bax expression). The expression of ER α and β in protein and mRNA levels was down-regulated by evodiamine according to data from immunoblotting and RT-PCR analysis. Overall, our results indicate that evodiamine mediates degradation of ER and induces caspase-dependent pathway leading to inhibit proliferation of breast cancer cell lines. It suggests that evodiamine may in part mediate through ER-inhibitory pathway to inhibit breast cancer cell proliferation.

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1 The e ect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats. 2 Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not a ected by the chronic administration of amphetamine. 3 Plasma CCK levels were increased dose-dependently by amphetamine. 4 Proglumide, a CCK receptor antagonist, prevented amphetamine-induced inhibition of gastric emptying and the decrease in GI transit in male rats. 5 The selective CCK A receptor antagonist, lorglumide, dose-dependently attenuated the amphetamineinduced inhibition of gastric emptying in male rats. In contrast, the selective CCK B receptor antagonist, PD 135,158, did not reverse the e ect of amphetamine on gastric emptying. 6 Both lorglumide and PD 135,158 reversed the inhibitory e ect of amphetamine on GI transit in male rats. 7 These results suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK.