The aim of the present study was to investigate the relaxatory function of adenosine receptor subtypes in rat urinary bladder, and if it is altered in the state of inflammation. The in vitro responses to the P1 receptor agonist adenosine were investigated in the presence of the general P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 1*10(-4)M). Experiments were performed on preparations from normal (healthy) rats and rats with cyclophosphamide (CYP; 100mg kg(-1) i. p.)-induced cystitis. The specific P1A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 1*10(-5)M) decreased the adenosine relaxatory response in normal bladders (-60%), but not in preparations from CYP pre-treated rats. Immunohistochemical findings support the hypothesis that the expression of P1A(1) receptors in the rat urinary bladder is decreased during cystitis. The adenosine-evoked relaxation was not affected by the specific P1A(2A) antagonist SCH 58261 (3*10(-7)M), neither in normal nor in CYP pre-treated rats. The relaxation to adenosine was, however, significantly increased by the specific P1A(3) antagonist MRS 1523 (1*10(-5)M) in preparations from both normal and CYP pre-treated rats, suggesting P1A(3) to be mediating bladder contraction. Thus, in the rat urinary bladder the relaxation to adenosine is mainly due to the P1A(1) receptor, while the P1A(3) receptor seems to be responsible for contractile responses. The DPCPX-resistant part of the relaxation is possibly due to the P1A(2B) receptor, the fourth subtype of the adenosine receptor family.

Department of Biochemical Sciences Faculty of Pharmacy Charles University Heyrovskeho 1203 CZ 50005 Hradec Kralove Czech Republic