Korean J Physiol Pharmacol.  2009 Dec;13(6):503-510. 10.4196/kjpp.2009.13.6.503.

Relaxation Patterns of Human Gastric Corporal Smooth Muscle by Cyclic Nucleotides Producing Agents

• Kim YC
• Choi W
• Sung R
• Kim H
• You RY
• Park SM
• Youn SJ
• Kim MJ
• Song YJ
• Xu WX
• Lee SJ
• Yun HY

• KMID: 2285388
• DOI: http://doi.org/10.4196/kjpp.2009.13.6.503

Abstract

To elucidate the mechanism of cyclic nucleotides, such as adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5' -cyclic monophosphate (cGMP), in the regulation of human gastric motility, we examined the effects of forskolin (FSK), isoproterenol (ISO) and sodium nitroprusside (SNP) on the spontaneous, high K+ and acetylcholine (ACh)-induced contractions of corporal circular smooth muscle in human stomach. Gastric circular smooth muscle showed regular spontaneous contraction, and FSK, ISO and SNP inhibited its phasic contraction and basal tone in a concentration-dependent manner. High K+ (50 mM) produced sustained tonic contraction, and ACh (10 micrometer) produced initial transient contraction followed by later sustained tonic contraction with superimposed phasic contractions. FSK, ISO and SNP inhibited high K+-induced tonic contraction and also ACh-induced phasic and tonic contraction in a reversible manner. Nifedipine (1 micrometer), inhibitor of voltage-dependent L-type calcium current (VDCC(L)), almost abolished ACh-induced phasic contractions. These findings suggest that FSK, ISO and SNP, which are known cyclic nucleotide stimulators, inhibit smooth muscle contraction in human stomach partly via inhibition of VDCCL.

Keyword

Gastricintestinal (GI) tract; Human stomach; Relaxation; Forskolin (FSK); Isoproterenol (ISO); Sodium nitorprusside (SNP); Voltage-dependent L-type calcium current (VDCC(L))

MeSH Terms

Acetylcholine
Adenosine
Calcium
Contracts
Forskolin
Guanosine
Humans
Isoproterenol
Muscle, Smooth
Nifedipine
Nitroprusside
Nucleotides, Cyclic
Relaxation
Stomach
Acetylcholine
Adenosine
Calcium
Forskolin
Guanosine
Isoproterenol
Nifedipine
Nitroprusside
Nucleotides, Cyclic

Figure

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  Fig. 1. Characterization of gastric corporal circular muscle motility in human. (A) Human gastric smooth muscle shows regular contraction with 0.3 g and 4.2 cycles/min (n=13). (B, C) High K+ and ACh produce tonic and phasic contraction in human stomach (n=7∼11).

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  Fig. 2. Inhibitory effect of forskolin (FSK), isoproterenol (ISO) and sodium nitroprusside (SNP) on spontaneous contraction of human stomach. (A) SNP (3 and 5 μM) inhibited spontaneous contraction and decreased basal tone of human stomach. FSK also inhibited spontaneous contraction and the inhibitory effects of FSK and SNP are summarized in (B). Inhibitory effect of ISO on spontaneous contraction of human stomach is also summarized in (C). Asterisks show a statistical significance (p<0.05).

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  Fig. 3. Effect of FSK, ISO and SNP on high K+-induced contraction in human stomach. (A) High K+ (50 mM) produced tonic contraction in human stomach, and it was inhibited by 3, 5 and 10 μM FSK to 53%, 51% and 23% of the control, respectively (n=3∼4). (B) 3, 5 and 10 μM SNP inhibited high K+ (50 mM)-induced contraction to 65%, 54% and 46% of the control, respectively (n=4∼5). Inhibitory effects of FSK, SNP and ISO on high K+ (50 mM)-induced contraction of human stomach are summarized in (C∼E). Asterisks show a statistical significance (p<0.05).

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  Fig. 4. Effects of FSK, ISO and SNP on acetylcholine (ACh)-induced contraction in human stomach. FSK, ISO and SNP inhibited ACh-induced contraction in a concentration-dependent manner. (A) FSK (3, 5 and 10 μM) inhibited ACh-induced phasic and tonic contraction (n=3∼5). Inhibitory effect of FSK on ACh-induced contraction is summarized in (B). Similar inhibitory effect on ACh-induced contraction by both SNP and ISO was observed, as shown in (C) and (D). Asterisks show a statistical significance (p<0.05).

Reference

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