Abstract
Objective
To investigate the presence, location and functional role of TMEM16A/anotamin-1 (Ano1) calcium-activated chloride channel (CaCC) in the penile of rats with diabetic erectile dysfunction.
Methods
Eight-week-old male Sprague-Dawley (SD) rats were administrated streptozotocin (diabetic) or citrate buffer (control) randomly. Erectile function was measured by cavernous nerve electrostimulation at 12th week after diabetes was induced. The effect of Ano1 specific inhibitor—T16Ainh-A01 on intracavernous pressure (ICP) was evaluated. Then the penile tissues were harvested for molecular exploration. Real-time PCR and Western Blotting were used to assess the expression of Ano1 in penile tissues. Immunofluorescent labelling of penile tissue allowed localization of Ano1. Cavernous smooth muscle cell (CSMC) was cultured in high glucose medium. The change of Ano1 was measured using Western Blotting. The proliferation of CSMC was evaluated by cell counting kit-8 (CCK-8).
Results
Erectile function was impaired in diabetic rats. The expression of Ano1 was increased in rats with diabetic erectile dysfunction at mRNA and protein levels. Immunofluorescent labelling revealed the presence of Ano1 mainly in cavernous smooth muscle cells. The inhibition of Ano1 increased the ICP of DED rats. High glucose in vitro enhanced the proliferation of CSMC and the expression level of Ano1.
Conclusions
Ano1 is expressed in rat penile tissue and is increased with diabetes mellitus. The inhibition of Ano1 increased the ICP of DED rats. The alerted Ano1 may be associated with diabetic erectile dysfunction. It is a potential therapy target for ED in the future.
Keywords: Diabetes, erectile dysfunction, TMEM16 A, calcium-activated chloride channel (CaCC)