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 F2α (PGF2α, 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. Preincubation 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 PGF2α (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 PGF2α (10−9−10−4 m) and carbachol (10−9−10−4 m) were not affected by pretreatment with l-NNA (10−4 m), as expressed by identical pD2 and Emax 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.