• Molecules and Cells
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• 제20권3호
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• pp.435-441
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• 2005

Classical transient receptor potential channels (TRPCs) are thought to be candidates for the nonselective cation channels (NSCCs) involved in pacemaker activity and its neuromodulation in murine stomach smooth muscle. We aimed to determine the role of TRPC4 in the formation of NSCCs and in the generation of slow waves. At a holding potential of -60 mV, $50{\mu}M$ carbachol (CCh) induced $I_{NSCC}$ of amplitude [$500.8{\pm}161.8pA$ (n = 8)] at -60 mV in mouse gastric smooth muscle cells. We investigated the effects of commercially available antibodies to TRPC4 on recombinant TRPC4 expressed in HEK cells and CCh-induced NSCCs in gastric smooth muscle cells. TRPC4 currents in HEK cells were reduced from $1525.6{\pm}414.4pA$ (n = 8) to $146.4{\pm}83.3pA$ (n = 10) by anti-TRPC4 antibody and $I_{NSCC}$ amplitudes were reduced from $230.9{\pm}36.3pA$ (n = 15) to $49.8{\pm}11.8pA$ (n = 9). Furthermore, $I_{NSCC}$ in the gastric smooth muscle cells of TRPC4 knockout mice was only $34.4{\pm}10.4pA$ (n = 8) at -60 mV. However, slow waves were still present in the knockout mice. Our data suggest that TRPC4 is an essential component of the NSCC activated by muscarinic stimulation in the murine stomach.

• The Korean Journal of Physiology
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• 제25권2호
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• pp.133-146
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• 1991

In order to elucidate systematically the effects of serotonin on gastric motility of guinea-pig, the contractile and electrical responses to serotonin were recorded using four kinds of muscle strips prepared from antral circular, antral longitudinal, fundic circular, and fundic longitudinal muscles. Experiments were performed using various methods including isometric contraction recording, transmural electrical field stimulation, junction potential recording, intracellular microelectrode technique, and partition stimulation method. The results were as follows: 1) The effect of serotonin on spontaneous contractions was inhibitory in the circular muscle strips of the antrum and fundus, while it was excitatory in the longitudinal muscle strips of the antrum and fundus. Serotonin changed mainly phasic contractions of both the circular and longitudinal muscle strips in the antrum, while it changed mainly tonic contractions of both the circular and longitudinal muscle strips in the fundus. 2) On the contractions induced by transmural nerve stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum, but it increased them in the other three groups of muscle strips(antral longitudinal, fundic circular, and fundic longitudinal). 3) On the contractions induced by direct muscle stimulation, serotonin decreased the amplitude in the circular muscle strips of the antrum and fundus. 4) In the fundic circular muscle strips serotonin potentiated excitatory junction potentials (EJPs), and in the antral circular muscle strips it evoked EJPs after inhibitory junction potentials(IJPS). 5) In the antral circular muscle strips serotonin did not affect the slow wave even at the disappearance of spontaneous contractions. On the contrary it increased the amplitude of the slow wave, when the spike component was potentiated and the second component was inhibited. 6) In the antral circular muscle strips the membrane potential was slightly hyperpolarized, but the membrane resistance was not changed. From the above results following conclusions could be made. 1) Serotonin inhibits spontaneous contractions of the circular muscle layer and it increases those of the longitudinal one, irrespective of the gastric region. 2) In the guinea-pig stomach there exists a serotoninergic facilitatory neuromodulation system which exerts its effect on cholinergically mediated contraction. 3) The excitation-contraction decoupling was observed in the effect of serotonin.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.139-150
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• 1993

We have reported that dopamine potentiates spontaneous contractions dose-dependently in guinea-pig antral circular muscle strips (Hwang et al, 1991). To clarify the underlying excitatory mechanism of dopamine on the gastric smooth muscle, the effects of dopamine on voltage-dependent $Ca^{2+}\;currents\;and\;Ca^{2+}\;-dependent\;K^+\;currents$ were observed in enzymatically dispersed guinea-pig gastric myocytes using the whole-cell voltage-clamp technique. Experiments were also done using isometric tension recording and conventional intracellular microelectrode techniques. 1) The effect of dopamine on the spontaneous contraction of antral circular muscle strips of the guinea-pig was excitatory in a dose-dependent manner, and was blocked by phentolamine, an ${\alpha}-adrenoceptor$ blocker. 2) The slow waves were not changed by dopamine. 3) The voltage-operated inward $Ca^{2+}$ current was not influenced by dopamine. 4) The $Ca^{2+}\;-dependent\;K^+$ outward current, which might reflect the changes of intracellular calcium concentration, was enhanced by dopamine. This effect was abolished by phentolamine. 5) The enhancing effect of dopamine on the $Ca^{2+}\;-dependent\;K^+$ current disappeared with heparin which is known to block the action of $InsP_3$. From these results, it is suggested that dopamine acts via $InsP_3-mediated\;Ca^{2+}$ mobilization from intracellular stores and such action potentiates the spontaneous contraction of guinea-pig gastric smooth muscle.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.275-282
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• 1999

Muscle strips and muscle cells from cat stomach were used to investigate whether spontaneously formed cyclic nucleotides were involved in the inhibition of gastric smooth muscle contraction. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), increased the levels of both cyclic GMP (cGMP) and cyclic AMP (cAMP) in resting state cells, while decreasing acetylcholine-induced muscle contraction. Under the influence of IBMX, SQ22536, an adenylyl cyclase inhibitor and methylene blue, a guanylyl cyclase inhibitor completely blocked increases in cAMP and cGMP respectively, without any effect on contraction. However, the combination of SQ22536 and methylene blue completely blocked increases in both cAMP and cGMP levels and stimulated contractions markedly even in the presence of IBMX. Muscle contraction inhibitors such as isoprenaline, vasoactive intestinal polypeptide and sodium nitroprusside also appeared to increase cyclic nucleotide levels which decreased contraction. Which nucleotide increased the most was dependent on the agonist used. Therefore, irrespective of the cyclic nucleotide class, the spontaneous formation of cyclic nucleotides should be considered in evaluating the mechanism of gastric smooth muscle relaxation.

• Journal of Gastric Cancer
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• 제21권2호
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• pp.213-219
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• 2021

Plexiform fibromyxoma (PF) of the stomach is a very rare mesenchymal tumor of the gastrointestinal tract. We report the first case of PF with 2 different growth patterns pathologically confirmed after surgical resection. The tumor was characterized microscopically as infiltrative; it demonstrated diffuse growth into the smooth muscle bundles of the muscularis propria and was also multinodular and plexiform within the myxoid stroma. Immunohistochemical analysis revealed that the tumor cells were positive or weakly positive for smooth muscle actin, vimentin, and H-caldesmon and negative for desmin, CD117, CD34, CK-20, Pan-CK, Dog1, S100, ER, PR, and CD10. No mutations of C-kit and platelet-derived growth factor receptor alpha were detected. No genetic disruption of glioma-associated oncogene homolog 1 was detected by fluorescence in situ hybridization. The final diagnosis of PF was mainly based on the morphological and immunohistochemical findings.

• The Journal of Korean Physical Therapy
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• 제14권4호
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• pp.454-474
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• 2002

Vasoactive intestinal peptide (VIP) is a very potent dilatator and a nonadrenergic, noncholinergic (NANC) neurotransmitter or neuromodulator in the peripheral and the central nervous systems. The mechanisms of action of VIP were examined in aortic circular and in uterine longitudinal smooth muscle strips of the rat. The effects of sympathetic neurotransmitter were investigated in gastric and aortic circular muscle strips of the mouse and the rat. The effects of silver spike point, SSP, low frequency electrical stimulations of VIP, sympathetic neurotransmitter and $\beta$-endorphin were examined in plasma, serum and 24h urine from the healthy volunteer. In gastric smooth muscle strips from the mouse, adrenergic neurotransmitter norepinephrine was inhibitory effected, followed by caused phasic and tonic contraction to the, muscrine receptor agonist carbachol and acetylcholine, respectively. In urine from the healthy volunteer, both norepinephrine and epinephrine were significantly decreased in continue type and low frequency (3 Hz) of SSP electrical stimulations. The contractile responses to S-HT in uterine longitudinal smooth muscle strips of the rats were completely decreased by a VIP 1 $\mu$M. The contractile responses to PGF2$\alpha$ were not decreased by a VIP. In plasma and serum from the healthy volunteer, both VIP and $\beta$-endorphin were significantly increased in continue type and low frequency (3 Hz) of SSP electrical stimulations. Therefore, this study demonstrate that VIP has the capacity to relax vascular or gastric smooth muscles in part by stimulating the generation of NO, and silver spike point low frequency electrical stimulation has the capacity both to decrease sympathetic neurotransmitters and to increase VIP, $\beta$-endorphin.

• The Korean Journal of Physiology
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• 제29권2호
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• pp.233-241
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• 1995

The nonapeptide bradykinin has been shown to exhibit an array of biological activities including relaxation/contraction of various smooth muscles. In order to investigate the effects of bradykinin on the contractility and the electrical activity of antral circular muscle of guinea-pig stomach, the isometric contraction and membrane potential were recorded. Also, using standard patch clamp technique, the $Ca^{2+}-activated$ K currents were recorded to observe the change in cytosolic $Ca^{2+}$ concentration. $0.4 {\mu}M$ bradykinin induced a triphasic contractile response (transient contraction-transient relaxation-sustained contraction) and this response was unaffected by pretreatment with neural blockers (tetrodotoxin, atropine and guanethidine) or with apamin. Bradykinin induced hyperpolarization of resting membrane potential and enhanced the amplitude of slow waves and spike potentials. The enhancement of spike potentials was blocked by neural blockers. Both the bradykinin-induced contractions and changes in membrane potential were reversed by the selective $B_2$-receptor antagonist $(N{\alpha}-adamantaneacetyl-_{D}-Arg-[Hyp, Thy,_{D}-Phe]-bradykinin)$. In whole-cell patch clamp experiment, we held the membrane potential at -20 mV and spontaneous and transient changes of Ca-activated K currents were recorded. Bradykinin induced a large transient outward current, consistent with a calcium-releasing action of bradykinin front the intracellular calcium pool, because such change was blocked by pretreatment with caffeine. Bradykinin-induced contraction was also blocked by pretreatment with caffeine. From these results, it is suggested that bradykinin induces a calciumrelease and contraction through the $B_{2}$ receptor of guinea-pig gastric smooth muscle. Enhancement of slow wave activity is an indirect action of bradykinin through enteric nerve cells embedded in muscle strip.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.84.2-84.2
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• 2006

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.425-430
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• 2014

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 $H_2$ receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through $H_2$ receptor and NO/sGC pathways.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.361-368
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• 1998

The spontaneous contractions of gastric smooth muscles are regulated by slow waves, which are modulated by both nervous system and humoral agents. This study was designed to examine the effects of prostaglandin $E_2$ ($PGE_2$) on the contractile and electrical activities of antral smooth muscles in guinea-pig stomach, using an intracellular recording technique. To elucidate the underlying mechanism for its effect on contractility, ionic currents were also measured using a whole-cell patch clamp method. The basal tone by $PGE_2$ was variable, whereas the magnitude of phasic contractions was reduced ($19.0{\pm}2.1%$, n=19). The resting membrane potentials were hyperpolarized ($-4.4{\pm}0.5%$ mV, n=10), and plateau potentials were lowered ($-2.9{\pm}0.5%$ mV, n=10). In most cases, however, the initial peak potentials of slow waves were depolarized more by $PGE_2$ than those of control. The frequency of the slows wave was increased from $5.7{\pm}0.2$ cycles/min to $6.5{\pm}0.2$ (n=22). Voltage-operated $Ca^{2+}$ currents were decreased by $PGE_2$ (n=5). Voltage-operated $K^+$ currents, both Ca-dependent and Ca-independent, were increased (n=5). These results suggest that $PGE_2$ plays an important role in the modulation of gastric smooth muscle activities, and its inhibitory effects on the contractility and activities of slow waves are resulted from both decrease of $Ca^{2+}$ currents and increase of $K^+$ currents.