Cisplatin up-regulates adenosine A(1) receptors in rat testes

Reactive oxygen species contribute to male infertility by reducing sperm fu nction. Our laboratory has recently demonstrated that reactive oxygen speci es stimulate the expression of adenosine A(1) receptor which confers cytopr otection in a variety of tissues. Since the adenosine A(1) receptor is high ly 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 alte r 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 p rotein by day 3. in addition, radioligand binding and Western blotting stud ies indicate an increase in testicular adenosine A(1) receptor in these rat s. Scatchard analysis of [H-3]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) bi nding data indicates a significant increase in adenosine A(1) receptor numb er (B-max) from 309 +/- 77 to 540 +/- 69 fmol mg(-1) protein in the cisplat in-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% followin g cisplatin treatment. These results indicate that cisplatin enhances adeno sine A(1) receptor expression in the rat testis, possibly through promotion of oxidative stress. (C) 1999 Elsevier Science B.V. All rights reserved.