Cholecystokinin-8s excites identified rat pancreatic-projecting vagal motoneurons

Autor: R. Alberto Travagli, F. Holly Coleman, Shuxia Wan
Rok vydání: 2007
Předmět:
medicine.medical_specialty
Patch-Clamp Techniques
Physiology
Autonomic Fibers
Preganglionic
Central nervous system
Action Potentials
Neuropeptide
Tetrodotoxin
Biology
Pancreatic Polypeptide
digestive system
Sincalide
Rats
Sprague-Dawley
Potassium Channels
Calcium-Activated
Paracrine signalling
Hormone Antagonists
Physiology (medical)
Internal medicine
medicine
Animals
Anesthetics
Local
Pancreas
Cholecystokinin
Motor Neurons
Dose-Response Relationship
Drug
Hepatology
Pancreatic Exocrine Secretion
digestive
oral
and skin physiology
Gastroenterology
Excitatory Postsynaptic Potentials
Vagus Nerve
Motor neuron
Rats
Receptor
Cholecystokinin A
Electrophysiology
Proglumide
Endocrinology
medicine.anatomical_structure
Animals
Newborn
Potassium
Calcium
hormones
hormone substitutes
and hormone antagonists
Brain Stem
Zdroj: American Journal of Physiology-Gastrointestinal and Liver Physiology. 293:G484-G492
ISSN: 1522-1547
0193-1857
DOI: 10.1152/ajpgi.00116.2007
Popis: It is known that cholecystokinin (CCK) acts in a paracrine fashion to increase pancreatic exocrine secretion via vagal circuits. Recent evidence, however, suggests that CCK-8s actions are not restricted to afferent vagal fibers, but also affect brain stem structures directly. Within the brain stem, preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) send efferent fibers to subdiaphragmatic viscera, including the pancreas. Our aims were to investigate whether DMV neurons responded to exogenously applied CCK-8s and, if so, the mechanism of action. Using whole cell patch-clamp recordings we show that perfusion with CCK-8s induced a concentration-dependent excitation in ∼60% of identified pancreas-projecting DMV neurons. The depolarization was significantly reduced by tetrodotoxin, suggesting both direct (on the DMV membrane) and indirect (on local synaptic circuits) effects. Indeed, CCK-8s increased the frequency of miniature excitatory currents onto DMV neurons. The CCK-A antagonist, lorglumide, prevented the CCK-8s-mediated excitation whereas the CCK-B preferring agonist, CCK-nonsulfated, had no effect, suggesting the involvement of CCK-A receptors only. In voltage clamp, the CCK-8s-induced inward current reversed at −106 ± 3 mV and the input resistance increased by 150 ± 15%, suggesting an effect mediated by the closure of a potassium conductance. Indeed, CCK-8s reduced both the amplitude and the time constant of decay of a calcium-dependent potassium conductance. When tested with pancreatic polypeptide (which reduces pancreatic exocrine secretion), cells that responded to CCK-8s with an excitation were, instead, inhibited by pancreatic polypeptide. These data indicate that CCK-8s may control pancreas-exocrine secretion also via an effect on pancreas-projecting DMV neurons.
Databáze: OpenAIRE
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