A possible role of the L-arginine-nitric oxide pathway in the modulation of cholinergic transmission in the guinea-pig taenia coli.
1. The role of the L-arginine-nitric oxide (NO) pathway for non-adrenergic, non-cholinergic (NANC) relaxation of the guinea-pig taenia coli was studied by recording isometric tension in response to transmural field stimulation (TMS). 2. In preparations precontracted with prostaglandin F2 alpha (PGF2 alpha, 10(-6) M), TMS induced frequency-dependent responses of the muscle strips which could be abolished by tetrodotoxin (10(-6) M). NG-nitro-L-arginine (L-NNA, 10(-4) M), an L-arginine analogue, and potent inhibitor of NO synthesis, stereospecifically inhibited maximum relaxations, but did not shift the frequency-response curve. Pre-incubation with NG-nitro-D-arginine (D-NNA, 10(-4) M), atropine (10(-6) M) plus L-NNA (10(-4) M), or atropine (10(-6) M) alone, had no influence on the frequency-response characteristics. 3. L-NNA (10(-7)-10(-4) M) concentration-dependently inhibited relaxations in PGF2 alpha (10(-6) M) precontracted strips in response to TMS, but did not abolish relaxations. Preincubation with L-arginine (10(-4) M) inhibited these effects of L-NNA. L-NNA (10(-4) M) had no effect on the inhibitory response during TMS in strips preincubated with atropine (10(-6) M). 4. The relaxation induced by sodium nitroprusside and forskolin (10(-9)-10(-4) M) was not influenced by L-NNA (10(-4) M) preincubation as expressed by identical pD2 and Emax values. 5. Contractions induced by PGF2 alpha (10(-9)-10(-4) M) and carbachol (10(-9)-10(-4) M) were not affected by pretreatment with L-NNA (10(-4) M), was expressed by identical pD2 and Emax values. 5. Contractions induced by PGFA (10-1- 10-4M) and carbachol (10-1 0-4 M) were not affected by pretreatment with L-NNA (10-4 M), as expressed by identical pD2 and Em. values.6. In conclusion, the L-arginine-NO pathway seems to play a role in the NANC innervation of the guinea-pig taenia coli. The inhibitory effect of NO or a NO-like compound depends on the integrity of the cholinergic pathways and it is proposed that this compound exerts its effects prejunctionally on cholinergic nerves, by inhibiting the release of acetylcholine.
Knudsen
M A
MA
Department of Obstetrics and Gynaecology, Aarhus Kommunehospital Hospital, Denmark.
Tøttrup
A
A
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000294:innervation*; D015237:Dinoprost / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D009599:Nitroprusside; D005576:Colforsin; D019335:Nitroarginine; D009569:Nitric Oxide; D001285:Atropine; D002217:Carbachol; D001120:Arginine; D015237:Dinoprost