A possible role of the L-arginine-nitric oxide pathway in the modulation of cholinergic transmission in the guinea-pig taenia coli

Abstract

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.