The role of α1-adrenoceptors and 5-HT1a receptors in the control of the micturition reflex in male anaesthetized rats

Abstract

1. The effects of the α1-adrenoceptor antagonists doxazosin (0.1-2 mg kg-1), RS-100329 (α1A; 0.01-1 mg kg-1), RS-513815 (Ro 151-3815, α1B; 0.3-3 mg kg-1) and BMY 7378 (α1D; 0.1-1 mg kg-1), the 5-HT1A receptor agonist, 8-OH-DPAT (0.03-0.3 mg kg-1) and antagonist WAY-100635 (0.03-0.3 mg kg-1) were investigated (i.v.) on the "micturition reflex" in the urethane anaesthetized male rat. 2. Reflex-evoked urethra contractions were most sensitive to the inhibitory action of RS-100329, followed by doxazosin, BMY 7378 and WAY-100635 and then RS-513815. The maximum inhibition was 66, 63, 54, 46 and 22% at doses of 0.3, 0.5, 0.3, 0.3 and 3 mg kg-1 respectively. 3. BMY 7378 and 8-OH-DPAT decreased, while WAY-100635 increased, the pressure threshold to induce bladder contraction. WAY-100635 (0.01 mg kg-1) blocked the effects of BMY 7378 (1 mg kg-1) on bladder pressure and volume threshold. 4. Doxazosin, RS-100329 and BMY 7378 had a similar potency in inducing a fall in arterial blood pressure while WAY-100635 only caused a fall at the highest dose. 5. Therefore, reflex-evoked urethral contraction involves the activation of α1A/1D-adrenoceptors, as BMY 7378 and RS-100329 are similarly potent in attenuating this effect. The ability of WAY-100635 to attenuate this contraction may suggest that 5-HT1A receptors are also involved. However, as this inhibition occurred at the highest dose of WAY-100635, which also caused a fall in arterial blood pressure; this effect is considered to be due to blockade of α1-adrenoceptors not 5-HT1A receptors. Nevertheless the initiation of the "micturition reflex" involves the activation of 5-HT1A receptors.