scholarly journals Electroacupuncture Stimulation at CV12 Inhibits Gastric Motility via TRPV1 Receptor

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Zhi Yu ◽  
Xin Cao ◽  
Youbing Xia ◽  
Binbin Ren ◽  
Hong Feng ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Knockout Mice ◽  
Functional Gastrointestinal Disorders ◽  
Inhibitory Effect ◽  
Gastrointestinal Disorders ◽  
Dependent Manner ◽  
Wild Type ◽  
Trpv1 Receptor ◽  
Alternative Approaches ◽  
Trpv1 Antagonist

Gastric dysmotility is one of the major pathophysiological factors in functional gastrointestinal disorders. Acupuncture, as one of the alternative approaches, is efficacious in the treatment of gastrointestinal motility disorders; however, the mechanism underlying its action is unclear. In the present study, we used both capsazepine, a TRPV1 antagonist, and TRPV1 knockout mice. Animals were divided into wild-type group (WT), capsazepine injection group (CZP, 0.5 mg/kg, i.p.), and TRPV1 knockout mice group (TRPV1−/−). Each of these three groups was divided into three subgroups, which were subjected to EA stimulation at acupoint Zhongwan (CV12) at a different intensity (1, 2, or 4 mA). We demonstrated that electroacupuncture at Zhongwan (CV12) markedly inhibited gastric motility at 2 and 4 mA in an intensity-dependent manner in wild-type mice. The inhibitory effect was also observed in capsazepine-injected and TRPV1−/−mice but was no longer intensity dependent, indicating that TRPV1 is partially involved in the electroacupuncture-mediated modulation of gastric motility.

scholarly journals Petasin and isopetasin reduce CGRP release from trigeminal afferents indicating an inhibitory effect on TRPA1 and TRPV1 receptor channels

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Johanna Kleeberg-Hartmann ◽  
Birgit Vogler ◽  
Karl Messlinger
Keyword(s):  
Inhibitory Effect ◽  
Transient Receptor Potential Channels ◽  
Mustard Oil ◽  
Root Extract ◽  
Dependent Manner ◽  
Trpv1 Receptor ◽  
Cgrp Release ◽  
Ganglion Neurons ◽  
Sites Of Action ◽  
The Impact

Abstract Background Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Methods We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay. Results Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels. Conclusions Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.

scholarly journals Effects of Different Local Moxibustion-Like Stimuli at Zusanli (ST36) and Zhongwan (CV12) on Gastric Motility and Its Underlying Receptor Mechanism

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-Shuai Su ◽  
Juan-Juan Xin ◽  
Zhao-Kun Yang ◽  
Wei He ◽  
Hong Shi ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Crucial Role ◽  
Pain Threshold ◽  
Facilitatory Effect ◽  
Response Relationship ◽  
Wild Type ◽  
Trpv1 Receptor ◽  
Thermal Pain ◽  
Intensity Response

The aim of this study was to explore the “intensity-response” relationship in local moxibustion-like stimuli- (LMS-) modulated gastric motility and its underlying receptor mechanism. Based on the thermal pain threshold (43°C), 41°C, 43°C, and 45°C LMS were separately applied to ST36 or CV12 for 180 s among ASIC3 knockout (ASIC3−/−) mice, TRPV1 knockout (TRPV1−/−) mice, and their homologous wild-type C57BL/6 mice (n=8in each group). Gastric motility was continuously measured by an intrapyloric balloon, and the amplitude, integral, and frequency of gastric motility during LMS were compared with those of initial activities. We found that both 43°C and 45°C LMS at ST36 induced significantly facilitated effect of gastric motilityP<0.05, while LMS at CV12 induced inhibited effectsP<0.05. 41°C LMS had no significant impact on gastric motility. Compared with C57BL/6 mice, the facilitatory effect at ST36 and inhibitive effect of LMS at CV12 were decreased significantly in TRPV1−/− mice (P<0.05;P<0.01) but not changed markedly in ASIC3−/− miceP>0.05. These results suggest that there existed an “intensity-response” relationship between temperature in LMS and its effects on gastric motility. TRPV1 receptor played a crucial role in the LMS-modulated gastric motility.

Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice

2007 ◽  
Vol 102 (1) ◽  
pp. 241-248 ◽  
Author(s):  
Akira Nakamura ◽  
Wei Zhang ◽  
Masashi Yanagisawa ◽  
Yasuichiro Fukuda ◽  
Tomoyuki Kuwaki
Keyword(s):  
Rem Sleep ◽  
Knockout Mice ◽  
Slow Wave Sleep ◽  
Ventilatory Response ◽  
Control Of Breathing ◽  
Dependent Manner ◽  
Wild Type ◽  
Vigilance State ◽  
State Dependent ◽  
Respiratory Parameters

Exogenous administration of orexin can promote wakefulness and respiration. Here we examined whether intrinsic orexin participates in the control of breathing in a vigilance state-dependent manner. Ventilation was recorded together with electroencephalography and electromyography for 6 h during the daytime in prepro-orexin knockout mice (ORX-KO) and wild-type (WT) littermates. Respiratory parameters were separately determined during quiet wakefulness (QW), slow-wave sleep (SWS), or rapid eye movement (REM) sleep. Basal ventilation was normal in ORX-KO, irrespective of vigilance states. The hypercapnic ventilatory response during QW in ORX-KO (0.19 ± 0.01 ml·min−1·g−1·%CO2−1) was significantly smaller than that in WT mice (0.38 ± 0.04 ml·min−1·g−1·%CO2−1), whereas the responses during SWS and REM in ORX-KO were comparable to those in WT mice. Hypoxic responses during wake and sleep periods were not different between the genotypes. Spontaneous but not postsigh sleep apneas were more frequent in ORX-KO than in WT littermates during both SWS and REM sleep. Our findings suggest that orexin plays a crucial role both in CO2 sensitivity during wakefulness and in preserving ventilation stability during sleep.

scholarly journals Petasin and Isopetasin Reduce CGRP Release from Trigeminal Afferents Indicating an Inhibitory Effect on TRPA1 and TRPV1 Receptor Channels

2021 ◽  
Author(s):  
Johanna Kleeberg-Hartmann ◽  
Birgit Vogler ◽  
Karl Messlinger
Keyword(s):  
Inhibitory Effect ◽  
Transient Receptor Potential Channels ◽  
Mustard Oil ◽  
Root Extract ◽  
Dependent Manner ◽  
Trpv1 Receptor ◽  
Cgrp Release ◽  
Ganglion Neurons ◽  
Sites Of Action ◽  
The Impact

Abstract Background: Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1.Methods: We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay. Results: Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels.Conclusions: Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.

scholarly journals Chemokine Receptor CXCR-2 Initiates Atrial Fibrillation by Triggering Monocyte Mobilization in Mice

Hypertension ◽  
2020 ◽  
Vol 76 (2) ◽  
pp. 381-392 ◽  
Author(s):  
Yun-Long Zhang ◽  
Hua-Jun Cao ◽  
Xiao Han ◽  
Fei Teng ◽  
Chen Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Bone Marrow ◽  
Chemokine Receptor ◽  
Knockout Mice ◽  
Bone Marrow Cells ◽  
Atrial Remodeling ◽  
Dependent Manner ◽  
Ang Ii ◽  
Wild Type ◽  
Chemokine Ligands

Atrial fibrillation (AF) is frequently associated with increased inflammatory response characterized by infiltration of monocytes/macrophages. The chemokine receptor CXCR-2 is a critical regulator of monocyte mobilization in hypertension and cardiac remodeling, but it is not known whether CXCR-2 is involved in the development of hypertensive AF. AF was induced by infusion of Ang II (angiotensin II; 2000 ng/kg per minute) for 3 weeks in male C57BL/6 wild-type mice, CXCR-2 knockout mice, bone marrow-reconstituted chimeric mice, and mice treated with the CXCR-2 inhibitor SB225002. Microarray analysis revealed that 4 chemokine ligands of CXCR-2 were significantly upregulated in the atria during 3 weeks of Ang II infusion. CXCR-2 expression and the number of CXCR2 + immune cells markedly increased in Ang II–infused atria in a time-dependent manner. Moreover, Ang II–infused wild-type mice had increased blood pressure, AF inducibility, atrial diameter, fibrosis, infiltration of macrophages, and superoxide production compared with saline-treated wild-type mice, whereas these effects were significantly attenuated in CXCR-2 knockout mice and wild-type mice transplanted with CXCR-2-deficient bone marrow cells or treated with SB225002. Moreover, circulating blood CXCL-1 levels and CXCR2 + monocyte counts were higher and associated with AF in human patients (n=31) compared with sinus rhythm controls (n=31). In summary, this study identified a novel role for CXCR-2 in driving monocyte infiltration of the atria, which accelerates atrial remodeling and AF after hypertension. Blocking CXCR-2 activation may serve as a new therapeutic strategy for AF.

Roles of prostaglandin E2-EP1 receptor signaling in regulation of gastric motor activity and emptying

2010 ◽  
Vol 299 (5) ◽  
pp. G1078-G1086 ◽  
Author(s):  
Sumito Mizuguchi ◽  
Takashi Ohno ◽  
Youichiro Hattori ◽  
Takako Ae ◽  
Tsutomu Minamino ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Motor Activity ◽  
Continuous Infusion ◽  
Knockout Mice ◽  
Smooth Muscles ◽  
Dependent Manner ◽  
Wild Type ◽  
Gastric Artery ◽  
Myoelectrical Activity ◽  
Gastric Motor Activity

It is widely accepted that the inhibition of gastric motor activity as well as the maintenance of gastric mucosal blood flow and mucous secretion are important for the homeostasis of the gastric mucosa. The present study was performed to ascertain whether or not endogenous PGs, which can protect the stomach from noxious stimuli, affect gastric motor activity and emptying. The myoelectrical activity of rat gastric smooth muscle was increased at intragastric pressures of over 2 cmH2O. Replacement of intragastric physiological saline with 1 M NaCl solution significantly increased PGI2 and PGE2 in stomach and suppressed the myoelectrical activity under a pressure of 2 cmH2O by 70%. Indomethacin inhibited the suppression of myoelectrical activity by 1 M NaCl. The myoelectrical activity under a pressure of 2 cmH2O was suppressed by continuous infusion of a selective EP1 agonist (ONO-DI-004, 3–100 nmol·kg−1·min−1) into the gastric artery in a dose-dependent manner, but not by that of the PGI receptor agonist beraprost sodium (100 nmol·kg−1·min−1). Suppression of myoelectrical activity with 1 M NaCl was inhibited by continuous infusion of a selective EP1 antagonist (ONO-8711, 100 nmol·kg−1·min−1) into the gastric artery. Furthermore, gastric emptying was tested in EP1 knockout mice and their wild-type counterparts. Gastric emptying was strongly suppressed with intragastric 1 M NaCl in wild-type mice, but this 1 M NaCl-induced suppression was not seen in EP1 knockout mice. These results suggest that PGE2-EP1 signaling has crucial roles in suppression of myoelectrical activity of gastric smooth muscles and inhibition of gastric emptying and that EP1 is an obvious target for drugs that control gastric emptying.

p53-dependent repression of the human MCL-1 gene encoding an anti-apoptotic member of the BCL-2 family: the role of Sp1 and of basic transcription factor binding sites in the MCL-1 promoter

2008 ◽  
Vol 389 (4) ◽  
pp. 383-393 ◽  
Author(s):  
Maciej Pietrzak ◽  
Monika Puzianowska-Kuznicka
Keyword(s):  
Transcription Regulation ◽  
Binding Sites ◽  
Microscopic Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Wild Type ◽  
Mobility Shift ◽  
P53 Expression ◽  
Hek 293 ◽  
Promoter Fragment

Abstract p53 regulates transcription of one anti-apoptotic and four pro-apoptotic members of the BCL-2 family, but nothing is known about the regulation of MCL-1, another anti-apoptotic member of this family, by p53. Confocal microscopic analysis of COS1, HEK 293 and HeLa cells transfected with a p53 expression plasmid demonstrated a decrease in the signal of endogenous MCL-1 compared to neighboring non-transfected cells. Transcription regulation assays showed that the 1826 bp human MCL-1 promoter fragment was repressed up to 30-fold by wild-type p53 in a dose-dependent manner. As shown by electrophoretic mobility shift assays, Sp1 binding to the sites located in the -295 to +16 MCL-1 promoter fragment was decreased in the presence of p53. However, the MCL-1 promoter devoid of all Sp1 binding sites was still repressed by p53, albeit 2-fold weaker than the wild-type promoter. Overexpression of Sp1 reduced p53-dependent repression of the MCL-1 promoter only up to 2.2-fold. Transcription regulation assays performed with MCL-1 promoter deletion mutants showed that most of the p53 inhibitory effect was mediated by the -41 to +16 bp promoter fragment containing binding sites only for TATA-binding protein and other basal transcription factors. We propose a novel, promoter-based mechanism by which p53 down-regulates expression of the anti-apoptotic MCL-1 protein.

scholarly journals P53-dependent suppression of the human calcyclin gene (S100A6): the role of Sp1 and of NFkappaB.

2008 ◽  
Vol 55 (3) ◽  
pp. 559-570 ◽  
Author(s):  
Weronika Króliczak ◽  
Maciej Pietrzak ◽  
Monika Puzianowska-Kuznicka
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Wild Type ◽  
Lower Efficiency ◽  
Wild Type P53 ◽  
Cell Cycle Deregulation ◽  
Cancer Tissues

Calcyclin (S100A6) is believed to participate in cell cycle control. It was, however, unclear if its expression depends on p53, a key regulator of apoptosis and cell cycle. We therefore performed transcription regulation assays in HeLa cells and found that wild type p53 suppressed the S100A6 promoter up to 12-fold in a dose-dependent manner. In contrast, the well-characterized V143A, R175H, R249S, and L344A p53 mutants cloned from human cancers suppressed this promoter with a 6 to 9-fold lower efficiency. All the sites mediating the p53-dependent suppression were contained in the -167 to +134 fragment of the S100A6 promoter. Separate overexpression of either Sp1 or of NFkappaB only partially counteracted the p53 inhibitory effect on the S100A6 promoter, while simultaneous overexpression of both these transactivators resulted in a complete abolishment of the p53 inhibitory effect on this promoter. Sp1 and NFkappaB binding to the probes resembling their putative binding sites present in the S100A6 promoter was decreased in the presence of wild type p53. We propose that the suppression of S100A6 is yet another mechanism by which p53 inhibits proliferation. Insufficient suppression of this gene by p53 mutants could well be responsible for calcyclin overexpression and cell cycle deregulation observed in cancer tissues.

scholarly journals Sex differences in GABAergic neurotransmission to rat DMV neurons

2019 ◽  
Vol 317 (4) ◽  
pp. G476-G483 ◽  
Author(s):  
Yanyan Jiang ◽  
Tanja Babic ◽  
R. Alberto Travagli
Keyword(s):  
Gastric Motility ◽  
Functional Gastrointestinal Disorders ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Gastrointestinal Disorders ◽  
Motor Nucleus ◽  
Estrus Cycle ◽  
Gastric Tone ◽  
Gabaergic Neurotransmission ◽  
Dorsal Motor Nucleus

Functional gastrointestinal disorders, including delayed gastric emptying and decreased gastric motility, are more prevalent in women, suggesting a potential role for circulating gonadal hormones, including estrogen. Gastric motility is tuned by the vagal inputs arising from the dorsal motor nucleus of the vagus (DMV), which is itself controlled by tonic GABAergic inputs. Estrogen increases GABA functions in various central nervous system areas; however, the effect of the estrus cycle in modulating GABAergic inputs onto DMV neurons, hence vagal control of gastric motility, has not been investigated. The aim of the present study was to test the hypothesis that GABAergic tone to DMV neurons, hence the vagal output to the stomach, varies according to sex and the estrus cycle. Experiments were performed on age-matched Sprague-Dawley male and virgin female rats; females were subdivided according to the high-estrogen (HE) or low-estrogen (LE) period of their cycle. Whole-cell patch-clamp recordings were made from gastric-projecting DMV neurons, and the response to perfusion with the GABAA receptor antagonist bicuculline was examined. The response of corpus and antrum tone and motility to bicuculline microinjected in the dorsal vagal complex, recorded via strain gauges sewn to the anterior gastric surface, was also assessed. Bicuculline increased the firing rate of DMV neurons, as well as gastric tone and motility, to a larger extent in HE compared with LE or male rats, suggesting a higher GABAergic tone in HE female rats. Taken together, the data support the hypothesis that GABAergic tone to DMV neurons varies according to sex and estrus cycle. NEW & NOTEWORTHY GABAergic neurotransmission to the dorsal motor nucleus of the vagus (DMV) plays a pivotal role in the modulation of gastric tone and motility. Gastric motility is reduced in women and may contribute to the higher incidence of functional gastrointestinal disorders. In the present study, we report that GABAergic tone to rat DMV neurons, hence vagal output to the stomach, varies according to sex and estrus cycle, and the GABAergic tone is increased during the high-estrogen period of the estrus cycle.

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