5-HT₄ receptors in isolated human corpus cavernosum?

Abstract

The novel serotonin subtype-4 (5-HT₄) receptor agonist, SC53116 (SC), produced a limited relaxation of noradrenaline (NA) pre-contracted human corpus cavernosum (CC) smooth muscle in vitro. This effect was not significantly attenuated by the 5-HT₄ antagonist SDZ250557 (SDZ). In the presence of (±) pindolol (1 μM) and methysergide (1 μM), employed to mask 5-HT₁ and β-adrenergic, and 5-HT₂ receptors respectively, SC failed to relax NA pre-contracted CC strips to a greater extent than saline. Functional cAMP dependent relaxation pathways were demonstrated by a significant reduction in NA induced tone by prostaglandin E₁ (PGE₁) and isopropylnoradrenaline (IPNA), the action of the latter compound was effectively eliminated in the presence of (±) pindolol. Relaxation of NA induced tone caused by the nitric oxide donor nitro-glycerine (NTG) was significant and similar in the absence and presence of the 5-HT and β-adrenergic antagonists. The results of this present study indicate that human corporal smooth muscle does not contain 5-HT₄ receptors and that, although compounds like SC act to relax non-vascular smooth muscle via cAMP dependent mechanisms, 5-HT₄ receptor agonists may be expected to be of limited utility in triggering cAMP dependent relaxation responses in human CC.