The Effects of the Antagonists of Muscarinic Acetylcholine Receptor Subtypes in Rat Brain on Urinary Bladder Contraction

BACKGROUND: Pontine micuturition center and storage center are controlled by upper brain. Pharmacological and molecular biological data indicate the distribution of muscarinic receptor subtypes in rat brain, however, the effect of central muscarinic cholinergic mechanisms on the bladder activity has not been evaluated. We investigated the diversity of effect of each subtype in rat brain. METHODS: The muscarinic agents such as muscarine (non-specific agonist), atropine (non-specific antagonist), pirenzepine (M1 receptor antagonist), AF-DX116 (M2 receptor antagonist) and 4-DAMP (M3 receptor antagonist) were administrated with intracerebroventricular injection (I.C.V. group) or intravenous injection (i.v. group). The drug effects on rhythmic bladder contraction were investigated. RESULTS: In I.C.V. group, the bladder contraction pressure were reduced by atropine, pirenzepine and 4-DAMP. The contraction time were shortened by pirenzepine and 4-DAMP but extended by AF-DX116. The contraction frequency was decreased by AF-DX116. Whereas AF-DX116 in i.v. group reduced the contraction pressure but did not cause any changes of the contraction time and the frequency. Other agents in i.v. group had same tendency with those of I.C.V. group except for intensity. CONCLUSION: That is to say AF-DX116 in I.C.V. group facilitate both micuturition center and storage center. In other words, these data indicate M2 receptor in rat brain inhibits both micurition and storage center. In addition, the effect of AF-DX116 in brain suggests that the development of new drug which proceed to central neuron system might provide a new treatment of neurogenic bladder.