Cyclic GMP-associated apamin-sensitive nitrergic slow inhibitory junction potential in the hamster ileum.
1. The mediators of non-adrenergic, non-cholinergic (NANC) inhibitory junction potentials (i.j.ps) in the circular smooth muscle cells of the hamster ileum were studied. 2. Electrical field stimulation (EFS; 0.5 ms duration, 15 V) of the intramural nerves with a train of five pulses at 20 Hz evoked a rapidly developing hyperpolarization (fast i.j.p.) followed by a sustained hyperpolarization (slow i.j.p.). 3. NG-nitro-L-arginine methyl ester (L-NAME; 50 - 200 microM) and NG-nitro-L-arginine (L-NNA; 50 - 200 microM), NO synthase inhibitors, inhibited or abolished the EFS-induced fast and slow NANC i.j.ps. The effects of these NO synthase inhibitors were reversed by L-arginine (5 mM) but not by D-arginine (5 mM). 4. Exogenously applied nitric oxide (NO; 1 - 100 microM) induced concentration-dependent hyperpolarizations. 5. Oxyhaemoglobin (5 - 50 microM), NO scavenger, inhibited only the slow i.j.p., and the NO-induced hyperpolarization. 6. 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxaline-1-one (ODQ; 10 microM) and cystamine (10 mM), guanylate cyclase inhibitors, inhibited only the slow i.j.p. Zaprinast (100 microM), a phosphodiesterase type V inhibitor, enhanced the amplitude and duration of the slow i.j.p. 7. Apamin (100 nM), a small conductance Ca2+-activated K+ channel blocker, inhibited only the slow i.j.p., and NO-induced hyperpolarization. A high concentration of 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo-cGMP; 1 mM)-induced membrane hyperpolarization which was blocked by apamin. 8. These results suggest that NO, or a related compound, may be the inhibitory transmitter underlying the apamin-sensitive NANC slow i.j.p. and cyclic GMP mediates the slow i. j.p. in the hamster ileum. It is also likely that NO, without involvement of guanylate cyclase is associated with the fast i.j.p.
Matsuyama
H
H
Department of Pathogenetic Veterinary Science, The United Graduate School, Gifu University, Gifu 501-1112, Japan.
Thapaliya
S
S
Takewaki
T
T
D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D006224:Cricetinae; D006152:Cyclic GMP / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D008647:Mesocricetus; D009569:Nitric Oxide / Q000502:physiology
D001030:Apamin; D009569:Nitric Oxide; D006152:Cyclic GMP