Spinal mechanism of micturition reflex inhibition by naftopidil in rats

Aim: We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. Methods: The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Key findings: Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1 mg) or IT (0.1 mu g) noradrenaline evoked bladder contractions, but IV (1 mg) or IT (0.01-1 mu g) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. Significance: Naftopidil inhibits the micturition reflex by blocking alpha 1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system. (C) 2014 Elsevier Inc. All rights reserved.