scholarly journals Vagal afferent CCK receptor activation is required for GLP ‐1‐ induced satiation

2021 ◽  
Author(s):  
Vasiliki Vana ◽  
Michelle K. Lærke ◽  
Jens F. Rehfeld ◽  
Myrtha Arnold ◽  
Oksana Dmytriyeva ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Vagal Afferent

scholarly journals CCK-Induced Reduction of Food Intake and Hindbrain MAPK Signaling Are Mediated by NMDA Receptor Activation

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2633-2646 ◽  
Author(s):  
Carlos A. Campos ◽  
Jason S. Wright ◽  
Krzysztof Czaja ◽  
Robert C. Ritter
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Vagal Afferents ◽  
Mapk Kinase ◽  
Vagal Afferent

The dorsal vagal complex of the hindbrain, including the nucleus of the solitary tract (NTS), receives neural and humoral afferents that contribute to the process of satiation. The gut peptide, cholecystokinin (CCK), promotes satiation by activating gastrointestinal vagal afferents that synapse in the NTS. Previously, we demonstrated that hindbrain administration of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists attenuate reduction of food intake after ip CCK-8 injection, indicating that these receptors play a necessary role in control of food intake by CCK. However, the signaling pathways through which hindbrain NMDA receptors contribute to CCK-induced reduction of food intake have not been investigated. Here we report CCK increases phospho-ERK1/2 in NTS neurons and in identified vagal afferent endings in the NTS. CCK-evoked phospho-ERK1/2 in the NTS was attenuated in rats pretreated with capsaicin and was abolished by systemic injection of a CCK1 receptor antagonist, indicating that phosphorylation of ERK1/2 occurs in and is mediated by gastrointestinal vagal afferents. Fourth ventricle injection of a competitive NMDA receptor antagonist, prevented CCK-induced phosphorylation of ERK1/2 in hindbrain neurons and in vagal afferent endings, as did direct inhibition of MAPK kinase. Finally, fourth ventricle administration of either a MAPK kinase inhibitor or NMDA receptor antagonist prevented the reduction of food intake by CCK. We conclude that activation of NMDA receptors in the hindbrain is necessary for CCK-induced ERK1/2 phosphorylation in the NTS and consequent reduction of food intake.

Peripheral bombesin induces gastric vagal afferent activation in rats

1996 ◽  
Vol 271 (6) ◽  
pp. R1584-R1593 ◽  
Author(s):  
E. Yoshida-Yoneda ◽  
T. J. O-Lee ◽  
J. Y. Wei ◽  
S. R. Vigna ◽  
Y. Tache
Keyword(s):  
Specific Binding ◽  
Receptor Activation ◽  
Gastric Distension ◽  
Specific Receptor ◽  
Afferent Activation ◽  
Gastric Smooth Muscle ◽  
Afferent Discharge ◽  
Vagal Afferent ◽  
Bombesin Antagonist ◽  
Stimulation Of

Bombesin's influence on gastric vagal afferent discharge (GVAD) was studied in urethan-anesthetized rats. Vehicle and peptides were injected intravenously at 30-min intervals. Cholecystokinin (CCK; 300 pmol) and bombesin (300 pmol) increased ongoing multiunit GVAD by 153 +/- 59 and 162 +/- 37%, respectively; similar increases were induced by a second injection of bombesin and CCK. The bombesin antagonist, ICI-216140, prevented bombesin-induced increase in GVAD, whereas the CCK response was not influenced. The CCK-A receptor antagonist devazepide reduced the activation of GVAD induced by bombesin from 107 +/- 11 to 63 +/- 6%, while abolishing the CCK response. Devazepide given alone or in combination with ICI-216140 did not modify gastric distension (3 ml)-induced increase in GVAD. Of 22 single units that were activated by gastric load (4 ml), 17 and 20 units responded also to bombesin (620 pmol) and CCK (870 pmol), respectively. Of the nine units that did not respond to gastric load, eight had an increase in GVAD induced by both bombesin and CCK. There was no specific binding of 125I-labeled [Tyr4]bombesin on cervical vagus, either intact or 24 h after ligation. These data suggest that intravenous bombesin-induced stimulation of GVAD is indirect and initially mediated through specific receptor activation influencing gastric smooth muscle and the release of CCK.

Cardiac Reflexes Conducted by Vagal Afferents in Normotensive and Renal Hypertensive Dogs

1976 ◽  
Vol 51 (s3) ◽  
pp. 353s-355s ◽  
Author(s):  
P. Kezdi
Keyword(s):  
Blood Pressure ◽  
Left Ventricular Pressure ◽  
Systemic Blood Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Balloon Occlusion ◽  
Ascending Aorta ◽  
Vagal Afferents ◽  
Vagus Nerves ◽  
Vagal Afferent

1. The renal sympathetic reflex responses to transient balloon occlusion of the descending aorta (systemic baroreceptor activation) and the ascending aorta (cardiac stretch-receptor activation) have been studied together with blood pressure increases after successive cutting of carotid sinus, aortic and vagus nerves in acute experiments in the dog. 2. Results from these experiments provide evidence for cardiac vagal afferent participation in the tonic regulation of systemic blood pressure. 3. In other experiments the reflex pressure-response curve of the isolated gracilis muscle at constant flow to transient ascending aorta occlusion was measured. This curve was moved to the right in renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left ventricular pressure in the former. 3. These findings indicate resetting of ventricular receptors in hypertensive animals.

Angiotensin II inhibition of Ca2+ currents is independent of ATR1 angiotensin II receptor activation in rat adult vagal afferent neurons

2005 ◽  
Vol 117 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Thaís Helena Moreira ◽  
Andréia Laura Rodrigues ◽  
Paulo Sérgio L. Beirão ◽  
Robson Augusto dos Santos ◽  
Jader Santos Cruz
Keyword(s):  
Angiotensin Ii ◽  
Receptor Activation ◽  
Afferent Neurons ◽  
Angiotensin Ii Receptor ◽  
Vagal Afferent

COVID-19 pathophysiology: interactions of gut microbiome, melatonin, vitamin D, stress, kynurenine and the alpha 7 nicotinic receptor: Treatment implications

2020 ◽  
Vol 3 (3) ◽  
pp. 322-345 ◽  
Author(s):  
George Anderson ◽  
Russel J Reiter
Keyword(s):  
Vitamin D ◽  
Coagulation Factors ◽  
Receptor Activation ◽  
Cytokine Induction ◽  
Aryl Hydrocarbon ◽  
Physiological Processes ◽  
Pulmonary Epithelial Cells ◽  
Vitamin D Levels ◽  
Complex Picture ◽  
Alpha 7

As data emerges on the pathophysiological underpinnings of severe acute respiratory syndrome coronavirus (SARS-CoV)-2, it is clear that there are considerable variations in its susceptibility and severity/fatality, which give indications as to its pathophysiology and treatment. SARS-CoV-2 modulatory factors include age, vitamin D levels, cigarette smoking, gender and ethnicity as well as premorbid medical conditions, including diabetes, cancer, obesity, cardiovascular disease, and immune-compromised conditions. A complex picture is emerging, with an array of systemic physiological processes interacting including circadian, immune, intestinal, CNS and coagulation factors. This article reviews data on SARS-CoV-2 pathoetiology and pathophysiology. It is proposed that a decrease in pineal and systemic melatonin is an important driver of SARS-CoV-2 susceptibility and severity, with the loss of pineal melatonin's induction of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) in pulmonary epithelial cells and immune cells being a powerful regulator of susceptibility and severity, respectively. Stress, including discrimination stress, and decreased vitamin D also regulate SARS-CoV-2, including via gut dysbiosis and permeability, with a resultant decrease in the short-chain fatty acid, butyrate, and increase in circulating lipopolysaccharide. Stress and cytokine induction of the kynurenine pathways, leads to aryl hydrocarbon receptor activation, which primes platelets for heightened activity, coagulation and thrombin production, thereby driving elevations in thrombin that underpin many SARS-CoV-2 fatalities. On the basis of these pathophysiological changes, prophylactic and symptomatic treatments are proposed, including the use of melatonin and α7nAChR agonism. 

Effect of κ-opiate receptor activation on the levels of insulin, somatostatin and blood glucose in man

1989 ◽  
Vol 120 (3_Suppl) ◽  
pp. S230
Author(s):  
A. PFEIFFER ◽  
V. SCHUSDZIARRA ◽  
V. BRANTL
Keyword(s):  
Blood Glucose ◽  
Opiate Receptor ◽  
Receptor Activation

Coaction of Electrostatic and Hydrophobic Interactions: Dynamic Constraints on Disordered TrkA Juxtamembrane Domain

2019 ◽  
Author(s):  
Zichen Wang ◽  
Huaxun Fan ◽  
Xiao Hu ◽  
John Khamo ◽  
Jiajie Diao ◽  
...  
Keyword(s):  
Single Molecule ◽  
Protein Function ◽  
Hydrophobic Interactions ◽  
Transmembrane Helix ◽  
Point Mutations ◽  
Salt Bridge ◽  
Receptor Activation ◽  
Membrane Dynamics ◽  
Juxtamembrane Domain ◽  
Joint Work

<p>The receptor tyrosine kinase family transmits signals into cell via a single transmembrane helix and a flexible juxtamembrane domain (JMD). Membrane dynamics makes it challenging to study the structural mechanism of receptor activation experimentally. In this study, we employ all-atom molecular dynamics with Highly Mobile Membrane-Mimetic to capture membrane interactions with the JMD of tropomyosin receptor kinase A (TrkA). We find that PIP<sub>2 </sub>lipids engage in lasting binding to multiple basic residues and compete with salt bridge within the peptide. We discover three residues insertion into the membrane, and perturb it through computationally designed point mutations. Single-molecule experiments indicate the contribution from hydrophobic insertion is comparable to electrostatic binding, and in-cell experiments show that enhanced TrkA-JMD insertion promotes receptor ubiquitination. Our joint work points to a scenario where basic and hydrophobic residues on disordered domains interact with lipid headgroups and tails, respectively, to restrain flexibility and potentially modulate protein function.</p>

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