title: N-methylhydroxylamine inhibits and M&B 22948 potentiates relaxations of the mouse anococcygeus to non-adrenergic, non-cholinergic field stimulation and to nitrovasodilator drugs.
abstract: 1. The effects of N-methylhydroxylamine (NMH) and of M&B 22948 on relaxations of the mouse anococcygeus to non-adrenergic, non-cholinergic (NANC) field stimulation and to a number of smooth muscle relaxant drugs were investigated. 2. Relaxations to NANC field stimulation (10 Hz; 60 s train) were reversibly blocked by NMH (1-5 mM), which also caused weak, transient reductions of carbachol (50 microM)-induced tone. N,N-dimethylhydroxylamine (2 mM) and hydroxylamine (5 microM) reduced tone to the same extent as NMH, but neither produced any inhibition of NANC relaxations. 3. M&B 22948 10 microM, which by itself reduced tone by 12%, potentiated submaximal but not maximal relaxations to NANC field stimulation; overall the log frequency-response curve was displaced to the left by a factor of 2. 4. Sodium nitroprusside (0.01-1 microM), hydroxylamine (0.5-100 microM), and nitric oxide (2-200 microM) all relaxed carbachol-induced tone; relaxations to submaximal concentrations of these nitrovasodilators were reduced in the presence of 2 mM NMH, and potentiated in the presence of 10 microM M&B 22948. 5. Neither NMH (2 mM) nor M&B 22948 (10 microM) affected relaxations induced by submaximal concentrations of vasoactive intestinal peptide (VIP; 1 microM), papaverine (10 microM), 3-isobutyl-1-methyl-xanthine (10 microM), or 8-bromo-cyclic guanosine monophosphate (100 microM); relaxations to adenosine 5'-triphosphate (ATP, 2 mM) were unaffected by M&B 22948, but were potentiated by NMH. 6. The selective inhibition by NMH, and potentiation by M&B 22948, of NANC and nitrovasodilator-induced relaxations of the mouse anococcygeus suggests that the NANC transmitter is neither VIP nor ATP, but resembles the nitrovasodilator drugs in its mode of action. The NANC transmission system is therefore similar to that recently described in the bovine retractor penis.
authors.affiliation: Pharmacology Group, Biomedical Sciences Division, Kings College London.
authors.forename: A
authors.initials: A
authors.lastname: Gibson
authors.forename: S
authors.initials: S
authors.lastname: Mirzazadeh
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D006898:Hydroxylamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011688:Purinones / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D006898:Hydroxylamines; D011688:Purinones; D014665:Vasodilator Agents; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C011145:zaprinast; C018338:N-methylhydroxylamine