title: Erectile function is improved in aged rats by PnTx2-6, a toxin from Phoneutria nigriventer spider venom.
abstract: BACKGROUND
  Age-associated erectile dysfunction (ED) involves a decrease in nitric oxide (NO) availability and impaired relaxation. PnTx2-6, a toxin from the Phoneutria nigriventer spider, has been demonstrated to improve erectile function via NO/cyclic guanosine monophosphate (cGMP) pathway. This spider's venom is characterized by several symptoms, including erection. PnTx2-6 has been implicated in this phenomenon. Animal venoms have been postulated as potential drugs to treat ED.
  
  
  OBJECTIVE
  PnTx2-6 toxin improves erectile function in aged rats via NO/cGMP. We investigated the effect of PnTx2-6 in the erectile function of aged rats.
  
  
  METHODS
  ED was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio during electrical field stimulation (EFS) of the pelvic ganglion of aged and adult rats (70 vs. 14 weeks). In functional studies, EFS-induced relaxation of corpus cavernosum (CC) strips were performed with or without PnTx2-6 (10-8M).
  
  
  RESULTS
  The decrease in erectile function associated with age was partially restored 15-20 minutes after injection of PnTx2-6 and further improved by sildenafil. PnTx2-6 enhanced EFS-induced relaxation, as well as cGMP levels in CC, from young and aged rats. Relaxation due to PnTx2-6 was further increased after 30 minutes incubation with Y-27632, a Rho-kinase inhibitor (10-6 M), in aging CC. Nitric oxide synthase (NOS) activity in aged and young cavernosal tissue was increased by incubation with PnTx2-6 (10 minutes). However, this toxin did not modify NOS expression.
  
  
  CONCLUSIONS
  PnTx2-6 improves penile relaxation in aged rats, via increased NOS activity and NO release, resulting in enhanced cGMP levels.
authors.affiliation: Department of Physiology, Georgia Health Sciences University, Augusta, GA, USA. keniapedrosa@gmail.com
authors.forename: Kenia P
authors.initials: KP
authors.lastname: Nunes
authors.forename: Haroldo A
authors.initials: HA
authors.lastname: Toque
authors.forename: Marcia H
authors.initials: MH
authors.lastname: Borges
authors.forename: Michael
authors.initials: M
authors.lastname: Richardson
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: de Lima
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006152:Cyclic GMP / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology*
chemical_list: D010455:Peptides; D013111:Spider Venoms; C540367:Tx2-6 protein, Phoneutria nigriventer; D009569:Nitric Oxide; D006152:Cyclic GMP