Non-Adrenergic Non-Cholivergic Responses of Guinea-Pig Fundic Circular Muscle

Whang, Il Soon; song, Chi Wook; Kang, Dong Hoon; Lee, Hong Sik; Lee, Sang Woo; Choi, Jae Hyun; Kim, Chang Duck; Ryu, Ho Sang; Hyun, Jin Hae

Abstract

BACKGROUND/AIMS: The neurogenic responses of gastrointestinal smooth muscles to electrical field stimulation(EFS) is biphasic, consisting firstly of cholinergic contraction, followed by a transient relaxation. It is well known that a transient relaxation does involve the inhibitory non- adrenergic non-cholinergic(NANC) systems. However, the exact nature of the neurotransmitter released by these neurons is controversial. This study was done to investigate the relaxing agents and their action mechanisms by the use of organ bath with platinum electrodes.
METHODS
In 10 guinea-pigs, muscle strips of fundus, 10mm x 2mm, were prepared in a circular axis. Isometric tension study was performed in 30ml organ baths containing Krebs bicarbonate buffer, tnaintatined at 37 'C and gassed with 5% CO and 95% Oz.
RESULTS
The fundic relaxation by EFS was suppressed by NG-nitro-L-arginine methyl ester(L-NAME) and nitric oxide(NO) synthase inhibitor, in a dose-dependent manner and these effects were reversed by L-arginine, precurssar of NO. Nitroprusside, NO-donor, suppressed the fundic basal tension largely. Methylene blue, inhibitor of guanylate cyclase, suppressed the fundic basal tension and decreased EFS-induced relaxations. Forskolin and isoprenaline, which are activators of adenylate cyclase, suppressed the fundic basal tension as rnuch as nitroprusside. Intracellularly permeable cGMP and cAMP pro- duced relaxations in the precontracted fundic muscle with noradrenaline. TEA, non-specific K' channel blocker, and aparnin, Ca ' activated K' channel blocker, increased the fundic basal tension and EFS-induced relaxations.
CONCLUSIONS
Above results indicate that NO is released upon stimulation of the NANC nerves in the guinea-pig fundic muscle and play a major role in the receptive relaxation of the fundus region. The release of NO is related with K' channel, and some other inhibitory agents may be involved in transient relaxation through modulative effects on cAMP or cGMP.