Journal List > Korean J Physiol Pharmacol > v.15(3) > 1025732

Lee, Kim, Kim, Myung, and Lee: The Relaxing Effect of α-Defensin 1 on the Adrenergic Responses of Rat Bladder

Abstract

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of α-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of α-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of α-defensin 1, the changes of effects on PE-induced contraction by α-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-κ:B inhibitors (PDTC; pyrrolidinedithio-carbamate and sulfasalazine). The contractile responses of PE (10–9∼10–4 M) were significantly decreased in some concentrations of α-defensin 1 (5×10–9 and 5×10–8 M). When strips were pretreated with NF-κB inhibitors (PDTC and sulfasalazine; 10–7 ∼ 10–6 M), the relaxing responses by α-defensin 1 pretreatment were disappeared. The present study demonstrated that α-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-κB pathway. Further studies in vivo are required to clarify whether α-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

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Fig. 1.
Typical representation of α-defensin-induced response of rat urinary bladder strip. No remarkable change was detected (W/O means wash out with PSS).
kjpp-15-143f1.tif
Fig. 2.
Effects of 10–9 M and 10–8 M α-defensin-pretreatment on the PE-induced contractures. The contractile responses were decreased and the effects were statistically significant (n=8, means p<0.05).
kjpp-15-143f2.tif
Fig. 3.
Effects of 10–9 M and 10–8 M α-defensin-pretreatment on the BCh-induced contractures. The tensions of contracture were rarely affected by the pretreatments (n=12).
kjpp-15-143f3.tif
Fig. 4.
Effects of concomitant pretreatment of 10–9 M α-defensin and PKC inhibitor and/or activator on PE-induced contractures. The concomitant pretreatment of α-defensin and other agents rarely affected the effects of defensin (n=8, means p<0.05).
kjpp-15-143f4.tif
Fig. 5.
Effects of concomitant pretreatment of 10–9 M α-defensin and NF-κB inhibitors on PE-induced contractures. The concomitant pretreatment of α-defensin and the inhibitors was almost completely reversed the effects of α-defensin (n=8, means p<0.05).
kjpp-15-143f5.tif
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