The role of spinal and brainstem adenosine receptors in the modulation of the volume-evoked micturition reflex in the unanesthetized rat.

The pharmacology of the spinal, supraspinal and peripheral adenosine receptor subtypes (A1, A2) and their influence on the volume-evoked micturition reflex (VEMR) was studied in a chronic unanesthetised rat model by cystometrography after intrathecal (i.t.), intracerebroventricular (i.c.v.) and intravenous (i.v.) injection. Intrathecally administered A1 adenosine agonist: N6-(L-2-phenylisopropyl)adenosine (R-PIA) and A2 adenosine agonist: 5'-(N-ethylcarboxamido)adenosine (NECA) were equally active with 1.0 nmol reliably producing an increase in the volume necessary to induce the VEMR. At a higher dose (3 nmol), a long-lasting blockade of the VEMR was produced by both agonists. These effects were reversed following intraperitoneal injection of caffeine, an adenosine antagonist. This inhibition of the VEMR outlasted the spinal antinociceptive action which we have previously reported for these two agonists. Contrary to the spinal effect of these agonists, i.c.v. (0.3-3 nmol) and i.v. (100-1000 nmol) injections of R-PIA and NECA resulted in a significant decrease in the volume required to evoke the VEMR. We conclude that at the spinal level a xanthine-sensitive adenosine receptor(s) inhibits the VEMR. Based on several indirect lines of evidence, we speculate that these effects are not mediated by an action on primary afferent input or directly on preganglionic neurons, but on an excitatory interneuronal link.