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Role of a Novel Tetrodotoxin-Resistant Sodium Channel in the Nitrergic Relaxation of Corpus Cavernosum from the South American Rattlesnake Crotalus Durissus Terrificus.
MedLine Citation:
PMID:  21477017     Owner:  NLM     Status:  Publisher    
Introduction.  Coitus in snakes may last up to 28 hours; however, the mechanisms involved are unknown. Aim.  To evaluate the relevance of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) system in snake corpus cavernosum reactivity. Methods.  Hemipenes were removed from anesthetized South American rattlesnakes (Crotalus durissus terrificus) and studied by light and scanning electronic microscopy. Isolated Crotalus corpora cavernosa (CCC) were dissected from the non-spiny region of the hemipenises, and tissue reactivity was assessed in organ baths. Main Outcome Measures.  Cumulative concentration-response curves were constructed for acetylcholine (ACh), sodium nitroprusside (SNP), 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272), and tadalafil in CCC precontracted with phenylephrine. Relaxation induced by electrical field stimulation (EFS) was also done in the absence and presence of N(ω) nitro-L-arginine methyl ester (L-NAME; 100 µM), 1H-[1, 2, 4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 µM) and tetrodotoxin (TTX; 1 µM). Results.  The hemipenes consisted of two functionally concentric corpora cavernosa, one of them containing radiating bundles of smooth muscle fibers (confirmed by α-actin immunostaining). Endothelial and neural nitric oxide synthases were present in the endothelium and neural structures, respectively; whereas soluble guanylate cyclase and PDE5 were expressed in trabecular smooth muscle. ACh and SNP relaxed isolated CCC, with the relaxations being markedly reduced by L-NAME and ODQ, respectively. BAY 41-2272 and tadalafil caused sustained relaxations with potency (pEC(50) ) values of 5.84 ± 0.17 and 5.10 ± 0.08 (N = 3-4), respectively. In precontracted CCC, EFS caused frequency-dependent relaxations that lasted three times longer than those in mammalian CC. Although these relaxations were almost abolished by either L-NAME or ODQ, they were unaffected by TTX. In contrast, EFS-induced relaxations in marmoset CC were abolished by TTX. Conclusions.  Rattlesnake CC relaxation is mediated by the NO-cGMP-PDE5 pathway in a manner similar to mammals. The novel TTX-resistant Na channel identified here may be responsible for the slow response of smooth muscle following nerve stimulation and could explain the extraordinary duration of snake coitus. Capel RO, Mónica FZ, Porto M, Barillas S, Muscará MN, Teixeira SA, Arruda AMM, Pissinatti, L, Pissinatti A, Schenka AA, Antunes E, Nahoum C, Cogo JC, de Oliveira MA, and De Nucci G. Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus. J Sex Med **;**:**-**.
Rodrigo O Capel; Fabíola Z Mónica; Marcovan Porto; Samuel Barillas; Marcelo Nicolás Muscará; Simone Aparecida Teixeira; André Moreira Martins Arruda; Lorenzo Pissinatti; Alcides Pissinatti; André A Schenka; Edson Antunes; César Nahoum; José Carlos Cogo; Marco Antonio de Oliveira; Gilberto De Nucci
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-7
Journal Detail:
Title:  The journal of sexual medicine     Volume:  -     ISSN:  1743-6109     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101230693     Medline TA:  J Sex Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 International Society for Sexual Medicine.
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil University Center IBMR, Rio de Janeiro, RJ, Brazil Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil Veterinary Course, University Center of Serra dos Órgãos, Teresópolis, RJ, Brazil Institute of Research and Development, University of Vale do Paraíba (UNIVAP), São José dos Campos, SP, Brazil.
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