Korean J Physiol Pharmacol.  2014 Oct;18(5):425-430. 10.4196/kjpp.2014.18.5.425.

H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO)

• Lee SE
• Kim DH
• Kim YC
• Han JH
• Choi W
• Kim CH
• Jeong HW
• Park SM
• Yun SJ
• Choi SY
• Sung R
• Kim YH
• Yoo RY
• Sun PH
• Kim H
• Song YJ
• Xu WX
• Yun HY
• Lee SJ

• KMID: 2285542
• DOI: http://doi.org/10.4196/kjpp.2014.18.5.425

Abstract

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K+ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.

Keyword

Circular smooth muscle; Corpus; H2 receptors; Histamine; Human stomach; Nitric Oxide (NO); Relaxation

MeSH Terms

Apamin
Glyburide
Guanylate Cyclase
Histamine
Humans
Muscle, Smooth*
Nerve Block
NG-Nitroarginine Methyl Ester
Nitric Oxide*
Ranitidine
Receptors, Histamine H2
Relaxation*
Tetraethylammonium
Apamin
Glyburide
Guanylate Cyclase
Histamine
NG-Nitroarginine Methyl Ester
Nitric Oxide
Ranitidine
Receptors, Histamine H2
Tetraethylammonium

Figure

• 

  Fig. 1 Effect of histamine on spontaneous phasic and tonic contractions of circular smooth muscle of human gastric corpus. (A) In human gastric corpus, histamine (10 µM) produced tonic relaxation of circular smooth muscle. However, it returned to basal contraction in a few minutes. In right panel, histamine-induced relaxation was summarized. (p<0.05) (B) Most tested tissues showed concentration-dependent tonic relaxation in circular smooth muscle of human gastric corpus. Histamine (1, 2, 5, and 10 µM) produced tonic relaxation from basal tone to -0.11 g, -0.12 g, -0.16 g, and -0.14 g, respectively. (C) In some cases, histamine produced both relaxation and contraction simultaneously in the same tissue. Histamine (0.5, 1, 2, 5, and 10 µM) increased the amplitude of phasic contraction to 241%, 223%, 262%, 306%, and 441% of the control respectively; n=3, 4, 4, 4, and 2, respectively).

• 

  Fig. 2 Histamine-induced relaxation in circular smooth muscle of human gastric corpus. (A, B) Histamine-induced tonic relaxation was not inhibited by pre- and post-application of glibenclamide which block ATP-sensitive K+ (KATP) channel. (C) Pretreatment of nerve blockers cocktail (NBC) and K+ channel blockers cocktail (KBC) did not affected histamine-induced tonic relaxation.

• 

  Fig. 3 Effect of NG-nitro-L-arginine methyl ester (L-NAME) on histamine-induced relaxation of circular smooth muscle in human gastric corpus. (A) Histamine-induced tonic relaxation was significantly inhibited by L-NAME. In the presence of L-NAME (100 µM), histamine-induced tonic relaxation was inhibited and/or reversed to tonic contraction. (B) In the presence of ODQ (10 µM) which inhibit soluble guanylyl cyclase (sGC), histamine-induced tonic relaxation was inhibited and/or reversed to tonic contraction.

• 

  Fig. 4 Effect of H2 receptor blockers on histamine-induced relaxation of circular smooth muscle in human gastric corpus. Effects of ranitidine (H2 receptor blocker) on histamine-induced tonic relaxation is shown. In the presence of ranitidine (0.5 mM), histamine-induced tonic relaxation was significantly suppressed compared to that of control (p<0.05).

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