cAMP and cGMP pathways modulate spontaneous contractile activity in human seminal vesicle smooth muscle
Abstract
Background: Human seminal vesicle (hSV) contractions contribute to seminal emission, but regulation of spontaneous oscillatory contractions (SOCs) between ejaculations remains incompletely understood. We examined how pharmacological enhancement of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling affects hSV contractile activity.
Methods: Isometric tension was recorded using isolated hSV strips. Area under the curve (AUC), contraction amplitude, and frequency were quantified. Rolipram (PDE4 inhibitor), mirabegron (β3-adrenoceptor agonist), sodium nitroprusside (SNP; nitric oxide donor), and tadalafil (PDE5 inhibitor) were examined under phenylephrine-induced precontraction. ADRB3, the gene encoding the β3-adrenoceptor, was assessed by reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results: Phenylephrine (0.1-300 μM) enhanced contractile activity in a concentration-dependent manner (EC50, 14.4 μM). Under phenylephrine precontraction (10 μM), rolipram, mirabegron, SNP, and tadalafil produced concentration-dependent relaxation, with IC50 values of 0.10, 2.0, 4.7, and 13 μM, respectively. Rolipram reduced both amplitude and frequency from low concentrations, mirabegron reduced amplitude at lower concentrations than frequency, and SNP and tadalafil reduced frequency at lower concentrations than amplitude. Vehicle control with dimethyl sulfoxide (DMSO) did not significantly affect these parameters. RT-qPCR showed…
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