Article date: May 2001
By: Rachel K Conley, Timothy J Williams, Anthony P D W Ford, Andrew G Ramage in Volume 133, Issue 1, pages 61-72
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
British Journal of Pharmacology (2001) 133, 61–72; doi:10.1038/sj.bjp.0704043
DOI: 10.1038/sj.bjp.0704043
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