title: PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP.
abstract: OBJECTIVE
  We designed a peptide, PnPP-19, comprising the potential active core of the Phoneutria nigriventer native toxin PnTx2-6. We investigated its role on erectile function, and its toxicity and immunogenicity.
  
  
  METHODS
  Erectile function was evaluated by the intracavernous pressure-to-mean arterial pressure ratio during electrical field stimulation on rat pelvic ganglia. Cavernous strips were contracted with phenylephrine and relaxation was induced by electrical field stimulation with or without PnPP-19 (10(-8) M). Activity on sodium channels was evaluated by electrophysiological screening of transfected channels on Xenopus oocytes and dorsal root ganglion cells. Antibodies were detected by indirect enzyme-linked immunosorbent assay in mice previously treated with the peptide. Histopathological studies were performed with mouse organs treated with different doses of PnPP-19.
  
  
  RESULTS
  PnPP-19 was able to potentiate erection at 4 and 8 Hz in vivo and ex vivo. It showed no toxicity and low immunogenicity in mice, and did not affect sodium channels or rat hearts. PnPP-19 increased cyclic guanosine monophosphate levels at 8 Hz. This effect was inhibited by L-NAME (10(-4) M). Erectile function was partially inhibited by 7-nitroindazole (10(-5) M), a selective inhibitor of neuronal nitric oxide synthase.
  
  
  CONCLUSIONS
  PnPP-19 potentiates erection in vivo and ex vivo via the nitric oxide/cyclic guanosine monophosphate pathway. It does not affect sodium channels or rat hearts and shows no toxicity and low immunogenicity. These findings make it a promising candidate as a novel drug in the therapy of erectile dysfunction.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Carolina Nunes
authors.initials: CN
authors.lastname: Silva
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Kenia Pedrosa
authors.initials: KP
authors.lastname: Nunes
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Fernanda Silva
authors.initials: FS
authors.lastname: Torres
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Juliana Silva
authors.initials: JS
authors.lastname: Cassoli
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Daniel Moreira
authors.initials: DM
authors.lastname: Santos
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Flávia De Marco
authors.initials: Fde M
authors.lastname: Almeida
authors.affiliation: Fundação Ezequiel Dias, Belo Horizonte, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Matavel
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Jader Santos
authors.initials: JS
authors.lastname: Cruz
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Arthur
authors.initials: A
authors.lastname: Santos-Miranda
authors.affiliation: Departmento de Ciências Fisiológicas, Universidade Federal Goiás, Goiânia, Brazil.
authors.forename: Allancer Divino C
authors.initials: AD
authors.lastname: Nunes
authors.affiliation: Departmento de Ciências Fisiológicas, Universidade Federal Goiás, Goiânia, Brazil.
authors.forename: Carlos Henrique
authors.initials: CH
authors.lastname: Castro
authors.affiliation: Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Brazil.
authors.forename: Ricardo Andrés
authors.initials: RA
authors.lastname: Machado de Ávila
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Chávez-Olórtegui
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Stephanie Stransky
authors.initials: SS
authors.lastname: Láuar
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Liza
authors.initials: L
authors.lastname: Felicori
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Jarbas Magalhães
authors.initials: JM
authors.lastname: Resende
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Elizabeth Ribeiro da Silva
authors.initials: ER
authors.lastname: Camargos
authors.affiliation: Fundação Ezequiel Dias, Belo Horizonte, Brazil.
authors.forename: Márcia Helena
authors.initials: MH
authors.lastname: Borges
authors.affiliation: Fundação Ezequiel Dias, Belo Horizonte, Brazil.
authors.forename: Marta Nascimento
authors.initials: MN
authors.lastname: Cordeiro
authors.affiliation: Toxicology and Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.affiliation: Toxicology and Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: melenalima@icb.ufmg.br.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: de Lima
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D009498:Neurotoxins; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010410:Penile Erection / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009479:Neuropeptides; D009498:Neurotoxins; C064022:Tx1 neurotoxin; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006152:Cyclic GMP
keywords: Phoneutria nigriventer; Tx2-6 protein; chemistry techniques; drug evaluation; penile erection; peptide; preclinical; synthetic