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

Young Chul Kim; Woong Choi; Rohyun Sung; Heon Kim; Ra Young You; Seon-Mee Park; Sei Jin Youn; Mi-Jung Kim; Young-Jin Song; Wen-Xie Xu; Sang Jin Lee; Hyo-Yung Yun

doi:10.4196/kjpp.2009.13.6.503

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Kim, Choi, Sung, Kim, You, Park, Youn, Kim, Song, Xu, Lee, and Yun: Relaxation Patterns of Human Gastric Corporal Smooth Muscle by Cyclic Nucleotides Producing Agents

Original Article

Korean J Physiol Pharmacol 2009;13(6):503-510.

Published online: 18 February 2009

DOI: https://doi.org/10.4196/kjpp.2009.13.6.503

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

Young Chul Kim^1,^∗, Woong Choi^2,³, Rohyun Sung⁴, Heon Kim⁵, Ra Young You¹, Seon-Mee Park⁶, Sei Jin Youn⁶, Mi-Jung Kim⁷, Young-Jin Song⁸, Wen-Xie Xu⁹, Sang Jin Lee¹, Hyo-Yung Yun^8,^†

¹Department of Physiology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

²Department of Pharmacology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

³BK21 Chungbuk Biomedical Science Center, Chungbuk National University, School of Medicine, Cheongju 361-763, Korea

⁴Department of Pathology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

⁵Department of Preventive Medicine, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

⁶Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

⁷Department of Pediatric, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

⁸Department of Surgery, Chungbuk National University College of Medicine, Cheongju 361-763, Korea

⁹Department of Physiology, College of Medicine, Shanghai Jiaotong University, 800 Dongchun Rd. Shanghai, 200240, P.R. China

^∗Corresponding to: Young Chul Kim, Department of Physiology, Chungbuk National University College of Medicine, 12, Gaeshin-dong, Heungduk-gu, Cheongju 361-763, Korea. (Tel) 82-43-261-2859, (Fax) 82-43-261-2859, (E-mail) physiokyc@chungbuk.ac.kr

^†Co-corresponding author: Hyo-Yung Yun, (Tel) 82-43-269-6032, (Fax) 82-43-266-6037, (E-mail) yunhyo@chungbuk.ac.kr

Received 18 November 2009 Revised 1 December 2009 Accepted 5 December 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 μM) 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 μM), 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 VDCC_L.

Keywords: Gastricintestinal (GI) tract, Human stomach, Relaxation, Forskolin (FSK), Isoproterenol (ISO), Sodium nitorprusside (SNP), Voltage-dependent L-type calcium current (VDCC_L)

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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).

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).

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).

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).

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