Tatsunori Okada, Hidetoshi Tozaki-Saitoh, Shunichi Kajioka, Kenichi Kato, Masaki Shiota, Eiji Kashiwagi, Masatoshi Eto
Pharmacological enhancement of cyclic nucleotide signaling reduced phenylephrine-induced hSV contractile activity. Rolipram showed the lowest apparent IC50. Mirabegron-sensitive relaxation together with ADRB3 transcript detection was compatible with possible β3-adrenoceptor involvement in hSV smooth muscle.
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 that ADRB3 was detected in seminal vesicle smooth muscle at lower levels than in detrusor smooth muscle and was not detected in seminal vesicle mucosa.
CONCLUSIONS: Pharmacological enhancement of cyclic nucleotide signaling reduced phenylephrine-induced hSV contractile activity. Rolipram showed the lowest apparent IC50. Mirabegron-sensitive relaxation together with ADRB3 transcript detection was compatible with possible β3-adrenoceptor involvement in hSV smooth muscle.