Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus

Autor: Marco Antonio de Oliveira, André Moreira Martins Arruda, Samuel Barillas, José Carlos Cogo, César R.D. Nahoum, Simone A. Teixeira, Lorenzo Pissinatti, Marcovan Porto, Marcelo Nicolas Muscará, Edson Antunes, Rodrigo O. Capel, Gilberto De Nucci, Alcides Pissinatti, Fabíola Z. Mónica, André Almeida Schenka
Rok vydání: 2011
Předmět:
Male
Pyridines
Endocrinology
Diabetes and Metabolism
Vasodilator Agents
Sodium Channels
Tadalafil
chemistry.chemical_compound
Endocrinology
Cyclic GMP
Oxadiazoles
biology
Crotalus
Callithrix
Psychiatry and Mental health
medicine.anatomical_structure
NG-Nitroarginine Methyl Ester
Tetrodotoxin
Sodium nitroprusside
Acetylcholine
medicine.drug
Sodium Channel Blockers
Nitroprusside
medicine.medical_specialty
Endothelium
Urology
In Vitro Techniques
FARMACOLOGIA
Nitric oxide
Internal medicine
Nitrergic Neurons
Quinoxalines
medicine
Animals
Phenylephrine
Cyclic Nucleotide Phosphodiesterases
Type 5
Dose-Response Relationship
Drug
Sodium channel
biology.organism_classification
Reproductive Medicine
chemistry
Microscopy
Electron
Scanning
Pyrazoles
Endothelium
Vascular
Nitric Oxide Synthase
Carbolines
Penis
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1743-6109
Popis: 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, Monica FZ, Porto M, Barillas S, Muscara 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 .
Databáze: OpenAIRE
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