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No evidence for a significant non‐nitrergic, hyperpolarising factor contribution to field stimulation‐induced relaxation of the mouse anococcygeus
Author(s) -
Fonseca Mario,
Uddin Nazim,
Gibson Alan
Publication year - 1998
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.0701862
Subject(s) - stimulation , neuroscience , chemistry , medicine , biology
The aim of the study was to determine whether a nerve‐derived hyperpolarizing factor (NDHF) might contribute to non‐adrenergic, non‐cholinergic (NANC) relaxations of the mouse anococcygeus when low concentrations of contractile agent are used to raise tone and low frequencies of field stimulation applied; such a non‐nitrergic NDHF has been proposed to contribute to NANC relaxations of the rat anococcygeus and guinea‐pig taenia coli. Phenylephrine (0.1–100 μ M ) produced concentration‐related contractions of the mouse isolated anococcygeus muscle; 0.2 μM phenylephrine (EC 26 ) was used to raise tone in subsequent experiments. Field stimulation (0.5, 1.0 and 5.0 Hz) produced frequency‐dependent relaxations of phenylephrine‐induced tone. In the presence of the nitric oxide synthase inhibitor L ‐N G ‐nitro‐arginine ( L ‐NOARG; 100 μ M ), the soluble guanylate cyclase inhibitor 1H‐[1,2,4]oxodiazolo[4,3‐a]quinoxalin‐1‐one (ODQ; 5 μ M ), or a combination of these two drugs, relaxations to field stimulation were abolished at all frequencies studied. Relaxations to sodium nitroprusside (0.01–5 μ M ) were unaffected by L ‐NOARG but strongly inhibited by ODQ; neither enzyme inhibitor affected relaxations to 8‐Br‐cyclic GMP (10 μ M ). Nifedipine (1 μ M ) reduced the contractile response to 0.2 μ M phenylephrine by 38%; however, it had no effect on NANC relaxations. It is concluded that NANC relaxations of the mouse anococcygeus are purely nitrergic and that there is no significant contribution from a putative NDHF.