Cisplatin up-regulates adenosine A(1) receptors in rat testes.
Eur J Pharmacol
; 382(1): 35-43, 1999 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-10556502
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Testículo
/
Cisplatino
/
Receptores Purinérgicos P1
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos