Neuromedin B Restores Erectile Function by Protecting the Cavernous Body and the Nitrergic Nerves from Injury in a Diabetic Rat Model

PLoS One. 2015 Jul 24;10(7):e0133874. doi: 10.1371/journal.pone.0133874. eCollection 2015.

Abstract

Erectile dysfunction (ED) is a major health problem worldwide and affects approximately 75% of diabetic patients, likely due to severely damaged cavernous body. While screening for cytokines produced by adipose tissue-derived stem cells, we detected neuromedin B (NMB). To explore a potential treatment option for ED, we examined whether NMB was capable of restoring erectile function. We also examined the potential mechanism by which NMB could restore erectile function. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. An adenovirus expressing NMB (AdNMB) was injected into the penis 6 weeks after STZ administration. Four weeks after the injection of AdNMB, erectile function, penile histology, and protein expression were analyzed. As assessed by the measurement of intracavernous pressure, AdNMB injection significantly restored erectile function compared with the injection of an adenovirus expressing green fluorescent protein. This restoration was associated with conservation of the cavernous body structure and neural nitric oxide synthase (nNOS)-expressing nerves, together with recovery of α-smooth muscle actin, vascular endothelial-cadherin, and nNOS expression. Furthermore, NMB significantly stimulated the survival of SH-SY5Y cells derived from human neuroblastoma tissue with characteristics similar to neurons. Collectively, these results suggested that NMB restored erectile function via protection of the cavernous body from injury and stimulation of the survival of the associated nerves. NMB may be useful to treat ED patients with a severely damaged cavernous body.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / physiopathology
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / physiopathology
  • Male
  • Neurokinin B / analogs & derivatives*
  • Neurokinin B / genetics
  • Neurokinin B / pharmacology
  • Neurokinin B / therapeutic use
  • Nitrergic Neurons / drug effects*
  • Penile Erection / drug effects*
  • Penile Erection / physiology
  • Penis / drug effects
  • Penis / physiopathology
  • Rats
  • Rats, Wistar

Substances

  • Neurokinin B
  • neuromedin B

Grants and funding

This work was supported by a grants-in-aid of the FUGAKU TRUST FOR MEDICINAL RESEARCH (http://www.smtb.jp/personal/entrustment/management/public/example/list.html), a Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan #24592422 (http://www.jsps.go.jp), and a Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan #24592423 (http://www.jsps.go.jp).