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

2008 ◽  
Vol 294 (5) ◽  
pp. G1210-G1218 ◽  
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.

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

2001 ◽  
Vol 280 (3) ◽  
pp. G406-G419 ◽  
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.

scholarly journals Distribution and localization of phosphatidylinositol 5-phosphate, 4-kinase alpha and beta in the brain

2020 ◽  
Author(s):  
Evan K. Noch ◽  
Isaiah Yim ◽  
Teresa A. Milner ◽  
Lewis C. Cantley
Keyword(s):  
Second Messengers ◽  
Immunohistochemical Analysis ◽  
Synaptic Function ◽  
Synaptic Membrane ◽  
Human Brain Tissue ◽  
Neuronal Marker ◽  
Axon Terminals ◽  
The Brain

AbstractPhosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) is critical for synaptic vesicle docking and fusion and generation of the second messengers, diacylglycerol and inositol-1,4,5-trisphosphate. PI-4,5-P2 can be generated by two families of kinases: type 1 phosphatidylinositol-4-phosphate 5-kinases, encoded by PIP5K1A, PIP5K1B and PIP5K1C, and type 2 phosphatidylinositol-5-phosphate 4-kinases, encoded by PIP4K2A, PIP4K2B, and PIP4K2C. While the roles of the type 1 enzymes in brain function have been extensively studied, the roles of the type 2 enzymes are poorly understood. Using selective antibodies validated by genetic deletion of pip4k2a or pip4k2b in mouse brain, we characterized the location of the enzymes, PI5P4Kα and PI5P4Kß, encoded by these genes. In mice, we demonstrate that PI5P4Kα is expressed in adulthood, whereas PI5P4Kß is expressed early in development. PI5P4Kα localizes to white matter tracts, especially the corpus callosum, and at a low level in neurons, while PI5P4Kß is expressed in neuronal populations, especially hippocampus and cortex. Dual labeling studies demonstrate that PI5P4Kα co-localizes with the oligodendrocyte marker, Olig2, whereas PI5P4Kß co-localizes with the neuronal marker, NeuN. Immunohistochemical subcellular distribution studies demonstrate that PI5P4Kα and PI5P4Kß are expressed in the early endosome system. Ultrastructural analysis demonstrates that both kinases are contained in axon terminals and dendritic spines adjacent to the synaptic membrane, which support a potential role in synaptic transmission. Immunohistochemical analysis of macaque and human brain tissue demonstrate a conserved pattern for PI5P4Kα and PI5P4Kß. These results highlight the diverse cell-autonomous expression of PI5P4Kα and PI5P4Kß and support further exploration into their role in synaptic function in the brain.

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

2009 ◽  
Vol 297 (5) ◽  
pp. G1028-G1034 ◽  
Author(s):  
Rumi Tanaka ◽  
Akio Inui ◽  
Akihiro Asakawa ◽  
Kaori Atsuchi ◽  
Koji Ataka ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Knockout Mice ◽  
New Method ◽  
Phase Iii ◽  
Wild Type ◽  
Motor Patterns ◽  
Fed State ◽  
Duodenal Motility ◽  
Manometric Method ◽  
Gastroduodenal Motility

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.

scholarly journals Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Andrea Mastinu ◽  
Marika Premoli ◽  
Giulia Ferrari-Toninelli ◽  
Simone Tambaro ◽  
Giuseppina Maccarinelli ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
History Of ◽  
Health And Disease ◽  
Pharmacological Potential ◽  
The Brain ◽  
Synthesis And Degradation

Abstract The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response. In this review a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main receptors, will be described. Furthermore, the pharmacological effects of cannabinoids will be outlined. An overview of the involvement of the endocannabinoidergic system in neuroinflammatory and metabolic pathologies will be made. Finally, particular attention will also be given to the new pharmacological entities acting on the two main receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the neuroinflammatory and metabolic mechanisms involved.

Relation between duodenal alkaline secretion and motility in fasted and sham-fed dogs

1986 ◽  
Vol 251 (5) ◽  
pp. G591-G596 ◽  
Author(s):  
S. J. Konturek ◽  
P. Thor
Keyword(s):  
Motor Activity ◽  
Vagal Stimulation ◽  
Secretory Activity ◽  
Phase Iii ◽  
Plasma Gastrin ◽  
Marked Rise ◽  
Sham Feeding ◽  
Duodenal Motility ◽  
Alkaline Secretion ◽  
Stimulation Of

A relation between duodenal myoelectric and motor activity and alkaline secretion has been investigated in conscious dogs under basal conditions and following vagal excitation with and without pretreatment with atropine or indomethacin. It was found that duodenal alkaline secretion shows typical periodicity in phase with the myoelectric or motor activity of the duodenum, reaching a peak during phase III and a nadir during phase I of the migrating motor complex (MMC). Sham feeding interrupted the motor and secretory MMC cycle and caused a prolonged increase in duodenal myoelectric or motor activity as well as a sudden and marked rise in duodenal alkaline secretion accompanied by a significant elevation in plasma gastrin and pancreatic polypeptide. Atropine and indomethacin abolished the motor and secretory duodenal cycles and reduced basal alkaline secretion significantly. Atropine abolished, whereas indomethacin increased duodenal myoelectric or motor activity during basal conditions and after vagal stimulation. Neither atropine nor indomethacin abolished sham feeding-induced duodenal alkaline secretion. We conclude that duodenal alkaline secretion fluctuates cyclically in phase with duodenal motility, vagal excitation results in a potent stimulation of duodenal motor and secretory activity, and the mechanism of vagally induced duodenal alkaline secretion is only partly cholinergic and does not involve endogenous generation of prostaglandins.

Stimulation of growth of a colon cancer cell line by gastrin

1986 ◽  
Vol 251 (5) ◽  
pp. G597-G601 ◽  
Author(s):  
C. J. Kusyk ◽  
N. O. McNiel ◽  
L. R. Johnson
Keyword(s):  
Motor Activity ◽  
Cancer Cell Line ◽  
Secretory Activity ◽  
Colon Cancer Cell Line ◽  
Phase Iii ◽  
Marked Rise ◽  
Sham Feeding ◽  
Duodenal Motility ◽  
Alkaline Secretion ◽  
Stimulation Of

A relation between duodenal myoelectric and motor activity and alkaline secretion has been investigated in conscious dogs under basal conditions and following vagal excitation with and without pretreatment with atropine or indomethacin. It was found that duodenal alkaline secretion shows typical periodicity in phase with the myoelectric or motor activity of the duodenum, reaching a peak during phase III and a nadir during phase I of the migrating motor complex (MMC). Sham feeding interrupted the motor and secretory MMC cycle and caused a prolonged increase in duodenal myoelectric or motor activity as well as a sudden and marked rise in duodenal alkaline secretion accompanied by a significant elevation in plasma gastrin and pancreatic polypeptide. Atropine and indomethacin abolished the motor and secretory duodenal cycles and reduced basal alkaline secretion significantly. Atropine abolished, whereas indomethacin increased duodenal myoelectric or motor activity during basal conditions and after vagal stimulation. Neither atropine nor indomethacin abolished sham feeding-induced duodenal alkaline secretion. We conclude that duodenal alkaline secretion fluctuates cyclically in phase with duodenal motility, vagal excitation results in a potent stimulation of duodenal motor and secretory activity, and the mechanism of vagally induced duodenal alkaline secretion is only partly cholinergic and does not involve endogenous generation of prostaglandins.

Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes and effects of two different insulins

2017 ◽  
Vol 66 (3) ◽  
pp. 661-668 ◽  
Author(s):  
Arun Sanyal ◽  
Kenneth Cusi ◽  
Mark L Hartman ◽  
Shuyu Zhang ◽  
Edward J Bastyr ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Fibrosis ◽  
Liver Fat ◽  
Phase Iii ◽  
Cytokeratin 18 ◽  
Alcoholic Fatty Liver ◽  
Link Type ◽  
Group Population

Data on cytokeratin-18 (K-18) and enhanced liver fibrosis (ELF) score in insulin-treated diabetes patients with non-alcoholic fatty liver disease (NAFLD) are limited. This study analyzed phase III data comparing basal insulin peglispro (BIL) and insulin glargine in type 1 (T1D), and type 2 diabetes (T2D) (insulin-naïve and insulin-treated). Alanine aminotransferase (ALT), K-18, ELF scores and liver fat content (LFC), measured by MRI, were obtained longitudinally. Baseline K-18 (U/L) was higher in T2D (range: 207‒247) than T1D (range: 148‒183), correlated with ALT in all populations (r (range) 0.264‒0.637, p<0.05), but with LFC only in T2D (r (range) 0.474‒0.586, p<0.05). K-18 increased significantly from baseline in BIL-treated, but not glargine-treated patients. Change from baseline (CFB) K-18 was significantly correlated with CFB in ALT in BIL-treated T2D populations. Baseline ELF scores were higher in T2D (range: 9.12‒9.20) than T1D (range: 8.24‒8.36), correlated with ALT in T1D only (0.209, p<0.05), and not correlated with LFC in any population. ELF scores increased significantly from baseline in BIL-treated but not glargine-treated patients. There were no correlations between CFB in LFC and ELF score at week 52 in any treatment group/population. In all BIL-treated populations, CFB in ALT and CFB in ELF score at week 52 were positively correlated. These data characterize associations of K-18 and ELF score with ALT and LFC in insulin-treated patients with T1D and T2D. Hepatopreferential insulins may be associated with increased K-18 and ELF scores but mechanisms and clinical significance are unknown. ClinicalTrials.gov identifiers are NCT01481779, NCT01435616, NCT01454284 and NCT01582451.

414 TYPE 1 AND TYPE 2 INTERFERONS AND INTERFERON- INDUCIBLE GENES ARE UPREGULATED IN THE BRAIN OF PATIENTS WITH HEPATITIS C AND SEVERE DEPRESSION

2009 ◽  
Vol 50 ◽  
pp. S156
Author(s):  
M. Trippler ◽  
K. Truebner ◽  
T. Bajanowski ◽  
S. Bein ◽  
G. Gerken ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Severe Depression ◽  
Inducible Genes ◽  
The Brain

Type 1 and Type 2 Aβ oligomers in the brain

2016 ◽  
Vol 39 ◽  
pp. S26
Author(s):  
Karen Ashe ◽  
Peng Liu ◽  
Miranda Reed ◽  
Marianne Grant ◽  
Colleen Forster ◽  
...  
Keyword(s):  
Aβ Oligomers ◽  
The Brain

Survival analysis according to disease subtype in AVAGAST: First-line capecitabine and cisplatin plus bevacizumab (bev) or placebo in patients (pts) with advanced gastric cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Manish A. Shah ◽  
Eric Van Cutsem ◽  
Yoon-Koo Kang ◽  
Shaker R. Dakhil ◽  
Taroh Satoh ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Proportional Hazards ◽  
Expression Profiles ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Asia Pacific ◽  
Dismal Prognosis ◽  
Type 3

5 Background: Gastric cancer (GC) is a heterogeneous disease that may be divided into distinct subtypes with different epidemiology, risk factors, and molecular expression profiles: proximal non-diffuse GC (type 1), diffuse GC (type 2), and distal non-diffuse GC (type 3). In clinical practice, GC subtypes are treated as a single disease. Regional efficacy differences were seen in AVAGAST: pts in Americas and Europe showed more evidence of benefit than Asia-Pacific pts. We analyzed outcomes in the phase III AVAGAST study according to GC subtype and region in order to test if GC subtype was prognostic of outcome and predictive of bev benefit. Methods: Pts were randomized and treated as previously described. The effect of treatment on overall survival (OS), measured by hazard ratio, was examined in an unplanned exploratory analysis using Cox proportional hazards models. Median OS was estimated using the Kaplan-Meier method. Results: 733 of 774 AVAGAST pts were included. Type 2 GC (52.1%) was more common than type 1 (9.5%) or type 3 (38.3%). Irrespective of treatment, pts with type 2 GC had worse outcome than type 3 GC (median OS 10.3 vs 11.7 mo; HR=0.82; 95% CI 0.68–1.00); non-Asian pts had the most dismal prognosis (8.0 vs 11.1 mo; HR=0.68; 95% CI 0.53–0.89). The table below describes the bev effect according to subtype. Non-Asian pts with GC type 2 and 3 appear to benefit from bev. Conclusions: In all regions, pts with type 3 GC had a better prognosis than type 2 GC. Bev therapy appeared to improve outcomes in non-Asian pts with type 2 and 3 GC. These data suggest that GC subtypes may be important predictors of pt outcome and warrant further prospective evaluation. [Table: see text]

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