title: Phoneutria nigriventer spider toxin Tx2-6 induces priapism in mice even after cavernosal denervation.
abstract: The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin. Denervated mice showed intense fibrosis of the cavernosal tissue as well as absence of synaptophysin IHC staining; surprisingly mice showed toxin-induced priapism when tested 15, 30 or 60 days after denervation. While sham-operated mice presented full priapism, denervated animals showed only partial priapism possibly due to the fibrosis. These results reveal that erection caused by Tx2-6 toxin may not depend on cavernosal nerves integrity. The effect of this toxin on sodium channels seem not directly involved in priapism as many toxins have identical effects but do not induce priapism. Discussion approaches the many different potential sites of intervention listed in the signaling cascades of NO/cGMP, RhoA/Rho-Kinase, as well as the emerging new gasotransmitter H2S. The pharmacological inhibition of Rho-kinase and toxin Tx2-6 have similar effects in vivo.
authors.affiliation: Instituto Butantan, Lab. of Pharmacology, São Paulo, Brazil. Electronic address: kath_ravelli@hotmail.com.
authors.forename: Katherine Garcia
authors.initials: KG
authors.lastname: Ravelli
authors.affiliation: Instituto Butantan, Lab. of Pharmacology, São Paulo, Brazil. Electronic address: dritramos@gmail.com.
authors.forename: Adriana de Toledo
authors.initials: AT
authors.lastname: Ramos
authors.affiliation: Instituto Butantan, Lab. of Pharmacology, São Paulo, Brazil. Electronic address: Luana.goncalves@butantan.gov.br.
authors.forename: Luana Baracho
authors.initials: LB
authors.lastname: Gonçalves
authors.affiliation: Instituto Butantan, Lab. of Immunochemistry, São Paulo, Brazil. Electronic address: fabio.magnoli@butantan.gov.br.
authors.forename: Fábio Carlos
authors.initials: FC
authors.lastname: Magnoli
authors.affiliation: Instituto Butantan, Lab. of Pharmacology, São Paulo, Brazil. Electronic address: lanfranco.troncone@butantan.gov.br.
authors.forename: Lanfranco Ranieri Paolo
authors.initials: LR
authors.lastname: Troncone
mesh_terms: D000818:Animals; D003714:Denervation; D007172:Erectile Dysfunction / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D010410:Penile Erection / Q000187:drug effects; D011317:Priapism / Q000139:chemically induced*; D013111:Spider Venoms / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D009479:Neuropeptides; D009498:Neurotoxins; D013111:Spider Venoms; C076902:Tx2 neurotoxin
keywords: Cavernous nerve; Denervation; In vivo; Mouse; Nitric oxide; Penile erection; Phoneutria nigriventer; Priapism; Prostatectomy; Spider toxin; Tx2-6