Functional and morphological examinations of P1A1 purinoceptors in the normal and inflamed urinary bladder of the rat

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; 100 mg kg− 1 i. p.)-induced cystitis. The specific P1A1 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 P1A1 receptors in the rat urinary bladder is decreased during cystitis. The adenosine-evoked relaxation was not affected by the specific P1A2A 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 P1A3 antagonist MRS 1523 (1 ⁎ 10− 5 M) in preparations from both normal and CYP pre-treated rats, suggesting P1A3 to be mediating bladder contraction. Thus, in the rat urinary bladder the relaxation to adenosine is mainly due to the P1A1 receptor, while the P1A3 receptor seems to be responsible for contractile responses. The DPCPX-resistant part of the relaxation is possibly due to the P1A2B receptor, the fourth subtype of the adenosine receptor family.