New method of manometric measurement of gastroduodenal motility in conscious mice: effects of ghrelin and Y2 depletion

Since no previous studies have reported dual measurements of stomach and duodenal motility in conscious mice, we developed a manometric method to measure the gastroduodenal motility in the physiological fed and fasted states of conscious mice. By this method we measured, for the first time, the gastroduodenal motility in Y2 knockout mice and analyzed the effects of ghrelin on the gastroduodenal motility in conscious mice. To evaluate this new method, we provide the comparison on the effects of CCK-8 examined by present and previous methods. In the fasted state of mice, phase III-like contractions with frequencies of 7.8 ± 0.5 contractions/h in the antrum and 6.6 ± 0.7 contractions/h in the duodenum were observed. This fasted pattern was disrupted and replaced by the fed pattern after feeding, with an increase of the motor index (MI) immediately after feeding. Intravenous injection of ghrelin induced the fasted pattern in the duodenum when injected in the fed state and increased %MI (114.3 ± 9.8%) compared with saline-injected controls (64.4 ± 9.6%) in the antrum. Intravenous injection of CCK-8 disrupted phase III-like contractions in both antrum and duodenum, which were replaced by fed-like motor patterns accompanied with the elevation of baseline pressure. In Y2 knockout mice, the frequency of phase III-like contractions was decreased in the antrum compared with wild-type mice and the immediate increase of MI after feeding seen in wild-type mice was disrupted in Y2 knockout mice. Our model provides a new method for studies of gastrointestinal motility in various mouse models, including transgenic and knockout ones.

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Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00549.2007 ◽

2008 ◽

Vol 294 (5) ◽

pp. G1210-G1218 ◽

Cited By ~ 52

Author(s):

Koji Ataka ◽

Akio Inui ◽

Akihiro Asakawa ◽

Ikuo Kato ◽

Mineko Fujimiya

Keyword(s):

Motor Activity ◽

Immunohistochemical Analysis ◽

Phase Iii ◽

Fed State ◽

Conscious Rats ◽

Duodenal Motility ◽

Gastroduodenal Motility ◽

The Brain

Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.

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Effects of central and peripheral urocortin on fed and fasted gastroduodenal motor activity in conscious rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.3.g406 ◽

2001 ◽

Vol 280 (3) ◽

pp. G406-G419 ◽

Cited By ~ 60

Author(s):

Naoki Kihara ◽

Masaki Fujimura ◽

Ikuo Yamamoto ◽

Etsuro Itoh ◽

Akio Inui ◽

...

Keyword(s):

Motor Activity ◽

Gastrointestinal Motility ◽

Truncal Vagotomy ◽

Central Action ◽

Motor Patterns ◽

Fed State ◽

Conscious Rats ◽

Duodenal Motility ◽

Gastroduodenal Motility ◽

Freely Moving

Since few previous studies have examined the effects of urocortin on physiological fed and fasted gastrointestinal motility, we administered urocortin intracerebroventricularly (icv) or intravenously (iv) in freely moving conscious rats and examined the changes in antral and duodenal motility. Icv and iv injection of urocortin disrupted fasted motor patterns of gastroduodenal motility, which were replaced by fed-like motor patterns. When urocortin was given icv and iv in the fed state, the motor activity remained like the fed patterns but % motor index (%MI) was decreased in the antrum and increased in the duodenum. Increase in the %MI in the duodenum induced by urocortin was shown as a nonpropagated event, since the transit of nonnutrient contents in the duodenum was decreased by icv and iv injection of urocortin. Changes in the gastroduodenal motility induced by icv injection of urocortin were abolished in animals with truncal vagotomy but not altered in animals with mechanical sympathectomy, suggesting that the vagal pathway may mediate the central action of urocortin. Neither urocortin antiserum nor α-helical CRF-(9–41) affected fed and fasted gastroduodenal motility, suggesting that endogenous urocortin is not involved in regulation of basal gastroduodenal motility.

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Effects of CCK receptor blockade on intestinal motor activity in conscious dogs

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1991.260.2.g315 ◽

1991 ◽

Vol 260 (2) ◽

pp. G315-G324 ◽

Cited By ~ 2

Author(s):

C. Niederau ◽

M. Karaus

Keyword(s):

Small Intestine ◽

Motor Activity ◽

Phase Ii ◽

Physiological Role ◽

Conscious Dogs ◽

Phase Iii ◽

Motor Patterns ◽

Fed State ◽

Specific Antagonist ◽

Cck Antagonist

This study employed a cholecystokinin (CCK) antagonist to evaluate whether endogenous CCK regulates fasted and fed motor patterns of the small intestine. Experiments were performed in six conscious dogs, each in duplicate. Motor activity was recorded by six strain-gauge transducers implanted along the small intestine. The effects of the CCK analogue caerulein and the CCK antagonist loxiglumide were studied in fasted and fed states. Computer analysis determined contractile frequency and area under contractions. Caerulein given as an intravenous bolus 30 min after phase III dose dependently caused a burst of phasic contractions preceded by a retrograde giant contraction. Continuous intravenous infusion of 10 mg.kg-1.h-1 loxiglumide completely abolished the effects of 10 ng/kg caerulein, which increases plasma CCK immunoreactivity to postprandial levels. Loxiglumide, at 10 mg.kg-1.h-1, markedly reduced the increase in phasic contractions due to a supraphysiological dose of 50 ng/kg caerulein to 14 +/- 6(SD)% of the control without loxiglumide (P less than 0.01). The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 micrograms/kg) was not altered by loxiglumide. Loxiglumide given in the fasted state decreased contractile frequency from 9.5 +/- 0.7 to 8.1 +/- 0.6/min and reduced the area under contractions during phase II to 81 +/- 5% of the control without loxiglumide (P less than 0.05). Loxiglumide also decreased contractile frequency during the fed state from 9.7 +/- 0.6 to 8.3 +/- 0.5/min and reduced the area under contractions to 78 +/- 6% of the control without loxiglumide (P less than 0.05). Thus loxiglumide acts as a specific antagonist of the actions of CCK on small intestinal motor activity in the dog. Loxiglumide, at a dose that abolishes actions of endogenous CCK, significantly decreased fasting motor activity during phase II. Loxiglumide also significantly reduced motor responses to feeding but did not prevent interruption of migrating motor complex cycle by a meal. CCK plays a physiological role in regulation of fasting and fed motor activity of small intestine, although other factors in addition to CCK mediate meal-induced motor activity.

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SK2 channel deletion reduces susceptibility to bupivacaine-induced cardiotoxicity in mouse

Human & Experimental Toxicology ◽

10.1177/09603271211010912 ◽

2021 ◽

pp. 096032712110109

Author(s):

H Chen ◽

Z Jin ◽

Z Fu ◽

F Xia

Keyword(s):

Regional Anesthesia ◽

Intravenous Injection ◽

Postoperative Analgesia ◽

Knockout Mice ◽

Qt Interval ◽

Qrs Complex ◽

Wild Type ◽

The Difference

Bupivacaine is frequently used for regional anesthesia and postoperative analgesia. However, an inadvertent intravenous injection can cause severe cardiotoxicity, manifesting as arrhythmia, hypotension, and even cardiac asystole. The mechanism of bupivacaine-mediated cardiotoxicity remains unclear. SK2 knockout mice (SK) and wild-type mice (WT) were divided into four groups, with 12 mice per group. We determined the difference in bupivacaine cardiotoxicity between SK2 knockout and WT mice by measuring the time to the first arrhythmia (Tarrhythmia) and the time to asystole (Tasystole). Secondary indicators of cardiotoxicity were the time from the beginning of bupivacaine infusion to 20% prolongation of the QT interval (TQT) and the time to 20% widening of the QRS complex (TQRS). Tarrhythmia and Tasystole were significantly longer in the SK-bupi group than in the WT-bupi group (both P < 0.05). TQT and TQRS were longer in the SK-bupi group than in the WT-bupi group (all P < 0.05). The time to 25%, 50%, and 75% reduction in HR in the SK-bupi group was significantly longer than in the WT-bupi group (all P < 0.05). Knocking out the SK2 channel can reduce bupivacaine-induced cardiotoxicity in the mouse.

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Neural modulation of canine duodenal bile acid delivery in the interdigestive and postprandial periods

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.264.2.g357 ◽

1993 ◽

Vol 264 (2) ◽

pp. G357-G366 ◽

Cited By ~ 1

Author(s):

R. B. Scott ◽

D. T. Tan

Keyword(s):

Bile Acid ◽

Phase Iii ◽

Gallbladder Emptying ◽

Fed State ◽

Duodenal Motility ◽

Neural Modulation ◽

Cephalic Phase ◽

Steady State Rate ◽

State Rate ◽

Algebraic Difference

The neural modulation of gallbladder filling-emptying and duodenal delivery of canine hepatic biliary output was studied in conscious dogs using transient cold blockade or transection of the cervical vagosympathetic nerves previously isolated in skin loops on either side of the neck. Gallbladder filling-emptying was defined as the algebraic difference between a steady-state rate of hepatic secretion [established by a continuous intravenous infusion of [14C]taurocholic acid (TCA)] and the duodenal rate of delivery of [14C]TCA (measured by duodenal marker perfusion). Duodenal motility was recorded manometrically. Experiments in the fasted and fed state were performed under control conditions, during cold blockade, and after transection of the cervical vagosympathetic nerves. Under control conditions: 1) during fasting, the majority of hepatic [14C]TCA output was stored in the gallbladder during the first half of the migrating myoelectric complex (MMC). An increased rate of duodenal delivery and partial gallbladder emptying occurred before phase III of the MMC. 2) Feeding induced an immediate increase in duodenal bile acid delivery and gallbladder emptying. After cold blockade or transection: 1) partial gallbladder emptying before phase III of the MMC was abolished. 2) The immediate postprandial increase in duodenal bile acid delivery and gallbladder emptying was abolished even when the animal received a continuous duodenal infusion of the duodenal aspirate of another fed animal (to control for the effect of impaired gastric emptying after cold blockade). In addition, cold blockade significantly reduced the effect of an exogenous infusion of cholecystokinin octapeptide on gallbladder emptying. These results suggest that neurons in the canine cervical vagosympathetic nerves play a major role in the regulation of rhythmic partial emptying of the gallbladder in the interdigestive period, coordinate a cephalic phase of postprandial gallbladder emptying, and are important in mediating the effects of cholecystokinin on the gallbladder during the gastric and enteric phases of postprandial gallbladder emptying.

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Characteristic motor patterns of phase II and behaviour of phase III in the fed state

Neurogastroenterology & Motility ◽

10.1111/j.1365-2982.1992.tb00099.x ◽

2008 ◽

Vol 4 (4) ◽

pp. 317-327 ◽

Cited By ~ 6

Author(s):

H. J. EHRLEIN ◽

H. R. SCHMID ◽

C. FEINLE

Keyword(s):

Phase Ii ◽

Phase Iii ◽

Motor Patterns ◽

Fed State ◽

Characteristic Motor

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Faculty Opinions recommendation of CB1 receptor knockout mice show similar behavioral modifications to wild-type mice when enkephalin catabolism is inhibited.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7003.464492 ◽

2006 ◽

Author(s):

Gyongyi Horvath

Keyword(s):

Knockout Mice ◽

Cb1 Receptor ◽

Wild Type

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IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01227-1 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Feixiang Chen ◽

Weihuang Liu ◽

Qiang Zhang ◽

Ping Wu ◽

Ao Xiao ◽

...

Keyword(s):

Bone Marrow ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Knockout Mice ◽

Inflammatory Markers ◽

Nerve Repair ◽

Peripheral Nerve Regeneration ◽

Wild Type ◽

Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

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Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice†

Biology of Reproduction ◽

10.1093/biolre/ioz149 ◽

2019 ◽

Cited By ~ 1

Author(s):

Naoki Ishii ◽

Takujiro Homma ◽

Jaeyong Lee ◽

Hikaru Mitsuhashi ◽

Ken-ichi Yamada ◽

...

Keyword(s):

Ascorbic Acid ◽

Superoxide Dismutase ◽

Coenzyme Q10 ◽

Knockout Mice ◽

Knockout Mouse ◽

Superoxide Dismutase 1 ◽

Wild Type ◽

Positive Effects ◽

Reproductive Ability ◽

Ascorbic Acid Supplementation

Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility.

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