No evidence for a significant non-nitrergic,hyperpolarising factor contribution to field stimulation-induced relaxation of the mouse anococcygeus |
| |
Authors: | Mario Fonseca Nazim Uddin Alan Gibson |
| |
Institution: | 1Pharmacology Group, Biomedical Sciences Division, King''s College London, Manresa Road, London SW3 6LX |
| |
Abstract: | - 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 μM) produced concentration-related contractions of the mouse isolated anococcygeus muscle; 0.2 μM phenylephrine (EC26) 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-NG-nitro-arginine (L-NOARG; 100 μM), the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1-one (ODQ; 5 μM), or a combination of these two drugs, relaxations to field stimulation were abolished at all frequencies studied. Relaxations to sodium nitroprusside (0.01–5 μM) were unaffected by L-NOARG but strongly inhibited by ODQ; neither enzyme inhibitor affected relaxations to 8-Br-cyclic GMP (10 μM).
- Nifedipine (1 μM) reduced the contractile response to 0.2 μM 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.
|
| |
Keywords: | Anococcygeus (mouse) 8-Br-cyclic GMP nerve derived hyperpolarizing factor nifedipine nitrergic L-NG-nitro-arginine IH-[ 1 2 4] oxodiazolo[ 4 3-a] quinoxalin-1-one phenylephrine sodium nitroprusside |
|
|