Investigation of the interaction between cholinergic and nitrergic neurotransmission in the pig gastric fundus

Abstract

1 The interaction between the cholinergic and nitrergic innervation was investigated in circular muscle strips of the pig gastric fundus. 2 In physiological salt solution containing 4610 76 M guanethidine, electrical ®eld stimulation (EFS; 40 V, 0.5 ms, 0.5 ± 32 Hz, 10 s at 4 min intervals) induced small transient relaxations at 0.5 ± 4 Hz, and large frequency-dependent contractions, sometimes followed by o -relaxations, at 8 ± 32 Hz. 3 In the presence of L-N G -nitroarginine methyl ester (L-NAME; 3610 74 M) or physostigmine (10 76 M), relaxations were reversed into contractions and contractions were enhanced. Physostigmine added to L-NAME further enhanced contractions, while addition of L-NAME to physostigmine had no additional e ect. O -relaxations were enhanced in the presence of L-NAME and physostigmine. L-NAME and physostigmine consistently increased basal tone. 4 Tissues contracted by 5-hydroxytryptamine or by acetylcholine responded to EFS in a similar way as in basal conditions and L-NAME reversed the relaxations at the lower stimulation frequencies into contractions and enhanced the contractions at the higher stimulation frequencies. 5 O -relaxations in the presence of L-NAME were partially reduced by a-chymotrypsin (10 U ml 71 ). 6 In the absence of physostigmine, the concentration-response curve to exogenous acetylcholine was not in¯uenced by L-NAME. 7 Contractions of the same amplitude induced by EFS at 4 Hz and by exogenous acetylcholine were either decreased or enhanced to the same extent by sodium nitroprusside (SNP; 10 75 M), depending upon the degree of relaxation by SNP. 8 These experiments suggest that endogenous nitric oxide interferes with cholinergic neurotransmission in the pig gastric fundus by functional antagonism at the postjunctional level. The interaction is independent of the degree of contraction.

M1Receptor-Mediated Nitric Oxide-Dependent Relaxation Unmasked in Stomach Fundus from M3Receptor Knockout Mice

“…The involvement of NO in the relaxant response observed in stomach fundus from M 3 receptor knockout mice was similar to the involvement of this signaling mechanism in other smooth muscle preparations (Kamata et al, 1993;Leclere and Lefebvre, 1998;Lefebvre and Vandekerckhove, 1998;Ny et al, 2000;Selemidis and Cocks, 2000;Baccari and Calamai, 2001).…”

“…Relaxation of the gastric fundus from multiple species has been well documented and may involve formation and release of peptides (Baccari and Calamai, 2001), prostanoids (Okada et al, 2000), and/or NO (Kamata et al, 1993;Leclere and Lefebvre, 1998;Lefebvre and Vandekerckhove, 1998;Ny et al, 2000;Selemidis and Cocks, 2000;Baccari and Calamai, 2001). Activation of NO release by cholinergic agonists has been reported in guinea pig (Wiklund et al, 1993) and cat ileum (Kortezova et al, 1998), rat jejunum (Olgart and Iversen, 1999), and human pulmonary arteries (Norel et al, 1996).…”

Effects of the Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester (L-NAME) on Antropyloroduodenal Motility and Appetite in Response to Intraduodenal Lipid Infusion in Humans

“…It should be recognized that the doses of L-NAME that have been shown to affect gastric motility and gastric emptying in animals are substantially greater than that used in our study (9)(10)(11)(13)(14)(15)(16)(17). For example, in dogs the amount of L-NAME that has been shown to slow gastric emptying and affect antropyloroduodena l motility is some 14 times greater than the dose we used (11,14).…”

“…Observations in animals suggest that nitric oxide (NO) may be an important modulator of gastroduodenal motility (9)(10)(11)(12)(13)(14)(15)(16)(17) and food intake (18)(19)(20)(21). The role of NO mechanisms is addressed optimally using speci c inhibitors of NO synthase (NOS), such as NG-L-arginine-methyl-ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA) (9-11, 13-17, 20).…”

Generalized loss of inhibitory innervation reverses serotonergic inhibition into excitation in a rabbit model of TNBS‐colitis

“…Several disturbances of gut function have been demonstrated in IBD, such as changes in sensory perception (Farthing & Lennard-Jones, 1978;Rao et al, 1987) and changes in gut motility (Snape et al, 1980;Loening-Baucke et al, 1989;Koch et al, 1990;Annese et al, 1997;Chrysos et al, 2001). These ®ndings re¯ect both in¯ammation-induced changes in the responsiveness of the smooth muscle and nerves.…”