title: Nitrergic inhibition of tachykininergic neuro-muscular transmission via cyclic GMP in the hamster ileum.
abstract: The present study was designed to explore the inhibitory mechanism by nitric oxide (NO) of the tachykininergic neuro-muscular transmissions in the hamster ileum. In the presence of guanethidine (1 µM), atropine (0.5 µM), nifedipine (0.1 µM) and apamin (100 nM), electrical field stimuli (EFS; 0.5 ms duration, 15 V) evoked non-adrenergic, non-cholinergic excitatory junction potentials (EJPs) in circular smooth muscle cells. The EJPs were markedly inhibited by the tachykinin NK1 receptor antagonists [D-Pro(4), D-Trp(7,9)]-SP(4-11) (3 µM). Both the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 200 µM) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM), did not affect on the resting membrane potentials, but enhanced the tachykininergic EJPs. In the presence of L-NAME (200 µM), exogenously applied NO (10 µM) and the membrane permeable analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP, 3 mM), significantly inhibited the tachykininergic EJPs. Application of EFS (0.5 msec duration, 15 V) with trains of 20 pulses at 20 Hz increased amount of released substance P (SP). The release of SP was further increased by the treatment of L-NAME or ODQ, but markedly reduced by exogenously applied NO and 8-Br-cGMP. These results suggest that the endogenous NO may inhibit the tachykininergic neuro-muscular transmissions by the decrease of SP release from the tachykininergic neurons, possibly through a guanylate cyclase-cGMP-dependent mechanism in the hamster ileum.
authors.affiliation: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, Gifu, Japan. mhayato@gifu-u.ac.jp
authors.forename: Hayato
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Unno
authors.forename: Seiichi
authors.initials: S
authors.lastname: Komori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Takewaki
mesh_terms: D000818:Animals; D006224:Cricetinae; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D007082:Ileum / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D008647:Mesocricetus; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D011810:Quinoxalines; D015320:Tachykinins; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D013373:Substance P; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester