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A possible role of the L‐arginine‐nitric oxide pathway in the modulation of cholinergic transmission in the guinea‐pig taenia coli
Author(s) -
Knudsen M.A.,
Tøttrup A.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14533.x
Subject(s) - carbachol , nitric oxide , taenia coli , sodium nitroprusside , endocrinology , medicine , atropine , tetrodotoxin , chemistry , nitroarginine , cholinergic , guinea pig , nitric oxide synthase , forskolin , arginine , stimulation , acetylcholine , biochemistry , amino acid
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 F 2α (PGF 2α , 10 −6 m ), TMS induced frequency‐dependent responses of the muscle strips which could be abolished by tetrodotoxin (10 −6 m ). N G ‐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 N G ‐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 PGF 2α (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 pD 2 and E max values. 5 Contractions induced by PGF 2α (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 pD 2 and E max 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.