Investigation of serotonin receptors in the isolated penile bulb of rats

Abstract

The aim of this study was to investigate serotonin (5-HT) receptors in the penile bulb, which have been suggested to play a role in penile erection. Serotonin (10⁻⁷–3 × 10⁻⁴ M) contracted penile bulbs in a concentration-dependent manner. Ketanserin (5-HT_2A antagonist, 10⁻⁹–10⁻⁷ M) and prazosin (α₁-adrenergic receptor blocker, 10⁻⁹–10⁻⁷ M) suppressed the lower and upper parts of concentration–response curves to 5-HT, respectively. Guanethidine (adrenergic neuron blocker, 5 × 10⁻⁵ M) reduced the responses to 5-HT at only 10⁻⁴ and 3 × 10⁻⁴ M concentrations. NAN-190 (5-HT_1A antagonist, 10⁻⁸, 10⁻⁷ M) shifted the concentration–response curve to the right with a reduction in the maximum response to 5-HT. While ondansetron (5-HT₃ antagonist, 10⁻⁶–10⁻⁵ M) and GR55562 (5-HT_1B/1D antagonist, 10⁻⁶–10⁻⁵ M) had no effect on the concentration–response curve to 5-HT. The 5-HT_1A agonist 8-OH-DPAT (10⁻⁷–3 × 10⁻⁴ M) contracted penile bulbs in a concentration-dependent manner with a lower pD₂ value than that of 5-HT. Sumatriptan (5-HT_1B/1D agonist, 10⁻⁸–10⁻⁴ M) did not produce any contractile response in the penile bulbs. Prucalopride, a selective 5-HT₄ agonist (R093877, 10⁻⁷–3 × 10⁻⁴ M) produced concentration-dependent relaxation in penile bulbs contracted by phenylephrine (10⁻⁵ M). 5-HT₄ agonists cisapride (10⁻⁷–10⁻⁴ M) and metoclopramide (10⁻⁷–3 × 10⁻⁴ M) also relaxed the tissue, concentration-dependently. Selective 5-HT₄ antagonists GR125487 (10⁻⁶–10⁻⁵ M) and GR113808 (10⁻⁶–10⁻⁵ M) slightly, but not significantly, decreased prucalopride- and cisapride-induced relaxation. Propranolol (β-adrenergic receptor blocker, 10⁻⁶–10⁻⁵ M) and L-NOARG (nitric oxide synthase inhibitor, 10⁻⁴ M) had no effect on prucalopride-induced relaxation. These results suggest the existence of α₁-adrenergic, 5-HT_1A and 5-HT_2A serotonergic receptors in the penile bulb of rats, which are responsible for 5-HT-induced contraction. Additionally, a serotonergic receptor resembling a 5-HT₄-type plays a role in the relaxation. The latter receptor is activated by 5-HT₄ agonists, but is not antagonized by 5-HT₄ antagonists.