Cisplatin up-regulates adenosine A(1) receptors in rat testes.
Reactive oxygen species contribute to male infertility by reducing sperm function. Our laboratory has recently demonstrated that reactive oxygen species stimulate the expression of adenosine A(1) receptor which confers cytoprotection in a variety of tissues. Since the adenosine A(1) receptor is highly expressed in the testis, the goal of this study was to determine whether this testicular adenosine A(1) receptor could also be regulated in vivo by reactive oxygen species. Cisplatin, a chemotherapeutic agent shown to alter testicular function, was used to generate reactive oxygen species in vivo. Testes obtained from Sprague-Dawley rats treated with cisplatin (8 mg kg(-1)) demonstrate increased lipid peroxidation and induction of heat shock protein by day 3. In addition, radioligand binding and Western blotting studies indicate an increase in testicular adenosine A(1) receptor in these rats. Scatchard analysis of [3H]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) binding data indicates a significant increase in adenosine A(1) receptor number (B(max)) from 309+/-77 to 540+/-69 fmol mg(-1) protein in the cisplatin-treated group. The respective equilibrium dissociation constants (K(d)s) were 3.2+/-1.5 and 3.0+/-0.7 nM for the control and cisplatin-treated groups, respectively. Northern blotting analysis of rat testicular poly (A)(+) RNA indicates two adenosine A(1) receptor transcripts migrating at 3.4 and 5.6 kb, whose combined levels were increased by 49.3+/-9.3% following cisplatin treatment. These results indicate that cisplatin enhances adenosine A(1) receptor expression in the rat testis, possibly through promotion of oxidative stress.
Bhat
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SG
Department of Pharmacology, Southern Illinois University School of Medicine, PO Box 19629, Springfield, IL 62794-9629, USA.
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Ramkumar
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D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015152:Blotting, Northern; D015153:Blotting, Western; D002945:Cisplatin / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress; D012313:RNA / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
D000970:Antineoplastic Agents; D006360:Heat-Shock Proteins; D018047:Receptors, Purinergic P1; D013739:Testosterone; D004958:Estradiol; D012313:RNA; D019204:GTP-Binding Proteins; D002945:Cisplatin