177 research outputs found
Recent advances and future research directions in neurogastroenterology and endocrinology recommendations of the National Commission on Digestive Diseases
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74710/1/j.1365-2982.2008.01212.x.pd
Delayed Gastric Emptying after Laparoscopic Anterior Highly Selective and Posterior Truncal Vagotomy
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75042/1/j.1572-0241.1995.tb09325.x.pd
Hypothalamic regulation of pancreatic secretion is mediated by central cholinergic pathways in the rat
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65667/1/j.1469-7793.2003.00571.x.pd
A possible role for Ca2+/calmodulin-dependent protein kinase IV during pancreatic acinar stimulusâsecretion coupling
AbstractCa2+/calmodulin-dependent protein kinases (CaMKs) are important intracellular mediators in the mediation of stimulusâsecretion coupling and excitationâcontraction coupling in a wide variety of cell types. We attempted to identify and characterize the functional roles of CaMK in mediating pancreatic enzyme secretion. Immunoprecipitation and immunoblotting studies using a CaMKII or CaMKIV antibody showed that rat pancreatic acini expressed both CaMKII and CaMKIV. Phosphotransferase activities of CaMKs were measured by a radioenzyme assay (REA) using autocamtide II, peptide Îł and myosin P-light chain as substrates. Although CaMKII and CaMKIV use autocamtide II as a substrate, peptide Îł is more efficiently phosphorylated by CaMKIV than by CaMKII. Intact acini were stimulated with cholecystokinin (CCK)-8, carbachol (CCh) and the high-affinity CCK-A receptor agonist, CCK-OPE, and the cell lysates were used for REA. CCK-8, CCh and CCK-OPE caused a concentration-dependent increase in CaMKs activities. When autocamtide II was used, maximal increases were 1.5â1.8-fold over basal (20.2±2.0 pmol/min/mg protein), with peaks occurring at 20 min after cell stimulation. In separate studies that used peptide Îł, CCK-8, CCh and CCK-OPE dose-dependently increased CaMKIV activities. Maximal increases were 1.5â2.4-fold over basal (30.7±3.2 pmol/min/mg protein) with peaks occurring at 20 min after cell stimulation. Peak increases after cell stimulation induced by peptide Îł were 1.8â2.8-fold higher than those induced by autocamtide II. CCK-8, CCh and CCK-OPE also significantly increased phosphotransferase activities of myosin light chain kinase (MLCK) substrate (basal: 4.4±0.7 pmol/min/mg protein). However, maximal increases induced by MLCK substrate were less than 10% of those occurring in peptide Îł. Characteristics of the phosphotransferase activity were also different between autocamtide II and peptide Îł. When autocamtide II was used, elimination of medium Ca2+ in either cell lysates or intact cells resulted in a significant decrease in the activity, whereas it had no or little effect when peptide Îł was used. This suggests that Ca2+ influx from the extracellular space is not fully required for CaMKIV activity and Ca2+ is not a prerequisite for phosphotransferase activity once CaMKIV is activated by either intracellular Ca2+ release or intracellular Ca2+ oscillations. The specific CaMKII inhibitor KN-62 (50 ÎŒM) had no effect on the CaMKIV activity and pancreatic enzyme secretion elicited by CCK-8, CCh and CCK-OPE. The specific MLCK inhibitor, ML-9 (10 ÎŒM), also did not inhibit CCK-8-stimulated pancreatic amylase secretion. In contrast, wide spectrum CaMK inhibitors, K-252a (1 ÎŒM) and KT5926 (3 ÎŒM), significantly inhibited CaMKIV activities and enzyme secretion evoked by secretagogues. Thus, CaMKIV appears to be an important intracellular mediator during stimulusâsecretion coupling of rat pancreatic acinar cells
Characterization of vagal pathways mediating gastric accommodation reflex in rats
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65599/1/j.1469-7793.1997.479be.x.pd
Electrophysiological identification of glucose-sensing neurons in rat nodose ganglia
The vagal afferent system is strategically positioned to mediate rapid changes in motility and satiety in response to systemic glucose levels. In the present study we aimed to identify glucose-excited and glucose-inhibited neurons in nodose ganglia and characterize their glucose-sensing properties. Whole-cell patch-clamp recordings in vagal afferent neurons isolated from rat nodose ganglia demonstrated that 31/118 (26%) neurons were depolarized after increasing extracellular glucose from 5 to 15 m m ; 19/118 (16%) were hyperpolarized, and 68/118 were non-responsive. A higher incidence of excitatory response to glucose occurred in gastric- than in portal vein-projecting neurons, the latter having a higher incidence of inhibitory response. In glucose-excited neurons, elevated glucose evoked membrane depolarization (11 mV) and an increase in membrane input resistance (361 to 437 MΩ). Current reversed at â99 mV. In glucose-inhibited neurons, membrane hyperpolarization (â13 mV) was associated with decreased membrane input resistance (383 to 293 MΩ). Current reversed at â97 mV. Superfusion of tolbutamide, a K ATP channel sulfonylurea receptor blocker, elicited identical glucose-excitatory but not glucose-inhibitory responses. Kir6.2 shRNA transfection abolished glucose-excited but not glucose-inhibited responses. Phosphatidylinositol bisphosphate (PIP 2 ) depletion using wortmannin increased the fraction of glucose-excited neurons from 26% to 80%. These results show that rat nodose ganglia have glucose-excited and glucose-inhibited neurons, differentially distributed among gastric- and portal vein-projecting nodose neurons. In glucose-excited neurons, glucose metabolism leads to K ATP channel closure, triggering membrane depolarization, whereas in glucose-inhibited neurons, the inhibitory effect of elevated glucose is mediated by an ATP-independent K + channel. The results also show that PIP 2 can determine the excitability of glucose-excited neurons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78667/1/jphysiol.2009.182147.pd
KATP channels in the nodose ganglia mediate the orexigenic actions of ghrelin
Ghrelin is the only known hunger signal derived from the peripheral tissues. Ghrelin overcomes the satiety signals evoked by anorexigenic molecules, such as cholecystokinin (CCK) and leptin, to stimulate feeding. The mechanisms by which ghrelin reduces the sensory signals evoked by anorexigenic hormones, which act via the vagus nerve to stimulate feeding, are unknown. Patch clamp recordings of isolated rat vagal neurons show that ghrelin hyperpolarizes neurons by activating K+ conductance. Administering a KATP channel antagonist or silencing Kir6.2, a major subunit of the KATP channel, abolished ghrelin inhibition in vitro and in vivo. Patch clamp studies show that ghrelin inhibits currents evoked by leptin and CCKâ8, which operate through independent ionic channels. The inhibitory actions of ghrelin were abolished by treating the vagal ganglia neurons with pertussis toxin, as well as phosphatidylinositol 3âkinase (PI3K) or extracellular signalâregulated kinase 1 and 2 (Erk1/2) small interfering RNA. In vivo gene silencing of PI3K and Erk1/2 in the nodose ganglia prevented ghrelin inhibition of leptinâ or CCKâ8âevoked vagal firing. Feeding experiments showed that silencing Kir6.2 in the vagal ganglia abolished the orexigenic actions of ghrelin. These data indicate that ghrelin modulates vagal ganglia neuron excitability by activating KATP conductance via the growth hormone secretagogue receptor subtype 1aâGαiâPI3KâErk1/2âKATP pathway. The resulting hyperpolarization renders the neurons less responsive to signals evoked by anorexigenic hormones. This provides a mechanism to explain the actions of ghrelin with respect to overcoming anorexigenic signals that act via the vagal afferent pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113677/1/tjp6781.pd
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