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Lau DH, Thompson CS, Bellringer JF, Thomas PJ, Mumtaz FH, Morgan RJ, Mikhailidis DP: Doxazosin and serotonin (5-HT) receptor (1A, 2A, and 4) antagonists inhibit 5-HT-mediated human cavernosal contraction. J Androl. 2006 Sep-Oct;27(5):679-85. Epub 2006 May 25.
Penile erection results from the balance between relaxation and contractile mechanisms of the corpus cavernosum. Only a few studies suggest a role for endogenous contractile agents such as 5-hydroxytryptamine (5-HT). Our aim was to confirm the possible role of 5-HT in human erection. The effect of 5-HT on human cavernosal tissues, as well as those of doxazosin (shown previously to have 5-HT inhibitory action), ketanserin (5-HT (2A) receptor antagonist), NAN-190 (5-HT (1A) receptor antagonist), and SB 203186 (5-HT (4) receptor antagonist) on 5-HT-mediated effects, were assessed using the organ bath technique, including electrical field stimulation study (EFS). Results are presented as median (mg/mg = mg contraction/mg of tissue). Consistent 5-HT-mediated (10 (-3) M) contractions were demonstrated (n = 18; 63 mg/mg). These contractions were inhibited with ketanserin by 90% (n = 8), NAN-190 by 68% (n = 12), and SB 203186 by 55% (n = 12). Doxazosin showed a similar 5-HT inhibitory action in a concentration-dependent manner (10 (-4) M; 94% reduction; n = 8, 10 (-6) M; 68.3% reduction; n = 8). Our EFS studies indicated the presence of neuronally derived 5-HT and that a majority of the nonnoradrenogenic contraction (54%) was mediated via 5-HT (2A) receptors. These findings suggest that 5-HT may play a role in the human detumescence process via 5-HT (1A), 5-HT (2A), and 5-HT (4) receptors. Neuronally released 5-HT is probably an important contractile neurotransmitter in the erectile process. Doxazosin, ketanserin, and 5-HT (1A) and 5-HT (4) receptor antagonists may be useful as part of combination therapy used to treat erectile dysfunction. |
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