Agmatine Induces Rat Prostate Relaxation through Activation of Peripheral Imidazoline I₂-Receptors

Objectives: The effect of agmatine on prostate contractility as well as the roles of imidazoline receptors and potassium channels in this action were studied using isolated Wistar rat prostate tissue. Methods: Rat prostate strips were pre-contracted with 1 μmol/L phenylephrine or 50 mmol/L KCl. The relaxation response to agmatine (1-100 μmol/L) was measured. The effects of imidazoline receptor blockers: efaroxan, BU224, KU14R; ATP-sensitive K⁺ channels (K_ATP) channel inhibitor: glibenclamide; cyclic AMP (cAMP) phosphodiesterase inhibitor: IBMX; or protein kinase A (PKA) inhibitor: H-89 on the agmatine-induced relaxation were studied. Results: Agmatine produced relaxation in prostate strips pre-contracted with phenylephrine or KCl in a dose-dependent manner. This relaxation was significantly reduced by BU224, a selective I₂ imidazoline receptor (IR) blocker, but not by I₁ or I₃ IR blockers (efaroxan, KU14R respectively). Moreover, the agmatine-induced relaxation was attenuated by glibenclamide and H-89, but enhanced by IBMX. Conclusion: The results suggest that agmatine causes rat prostate relaxation by activation of the I₂ IR, which opens K_ATP channels through cAMP/PKA pathway.