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Inhibition of neuroeffector transmission in human vas deferens by sildenafil
Author(s) -
Medina Pascual,
Segarra Gloria,
Torondel Belén,
Chuan Pascual,
Domenech Cristina,
Vila José M,
Lluch Salvador
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703657
Subject(s) - zaprinast , vas deferens , sildenafil , iberiotoxin , sodium nitroprusside , charybdotoxin , medicine , endocrinology , tetraethylammonium , chemistry , neuroeffector , pharmacology , nitric oxide , potassium channel , receptor , potassium , organic chemistry , guanylate cyclase
Sildenafil (0.1–30 μ M ), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1–100 μ M ), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1–100 μ M ) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxaline‐1‐one (ODQ) (1–30 μ M ) but it was abolished by the K + channel blockers tetraethylammonium (TEA, 1 m M ), iberiotoxin (0.1 μ M ) and charybdotoxin (0.1 μ M ). Sildenafil, zaprinast and SNP did not affect the contractions induced by noradrenaline. SNP (10 μ M ) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10 μ M ) and zaprinast (100 μ M ). ODQ (10 μ M ) inhibited the increase in cyclic GMP. Sildenafil inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large‐conductance Ca 2+ ‐activated K + channels. British Journal of Pharmacology (2000) 131 , 871–874; doi: 10.1038/sj.bjp.0703657