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Am J Physiol Regul Integr Comp Physiol ; 283(6): R1303-13, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12388458

ABSTRACT

Imaging fluorescent measurements with fura 2 were used to examine cytosolic calcium signals induced by sulfated CCK octapeptide (CCK-8) in dissociated vagal afferent neurons from adult rat nodose ganglia. We found that 40% (184/465) of the neurons responded to CCK-8 with a transient increase in cytosolic calcium. The threshold concentration of CCK-8 for inducing the response varied from 0.01 to 100 nM. In most neurons (13/16) the response was eliminated by removing extracellular calcium. Depleting intracellular calcium stores with thapsigargin slightly augmented the response. Most neurons were unresponsive to nonsulfated CCK-8. The response was eliminated by the CCK-A receptor antagonist lorglumide. Low concentrations of JMV-180 had no effect; however, high concentrations of JMV-180 reduced responses to CCK-8. These results demonstrate that CCK acts at the low-affinity site of the CCK-A receptor to trigger the entry of extracellular calcium into vagal afferent neurons. Increased cytosolic calcium may participate in acute activation of vagal afferent neurons, or it may initiate long-term changes, which modulate future neuronal responses to sensory stimuli.


Subject(s)
Calcium/metabolism , Cholecystokinin/pharmacology , Intracellular Fluid/drug effects , Neurons, Afferent/drug effects , Neurons, Afferent/metabolism , Sincalide/analogs & derivatives , Animals , Cholecystokinin/administration & dosage , Cholecystokinin/analogs & derivatives , Cholecystokinin/antagonists & inhibitors , Dose-Response Relationship, Drug , Fura-2 , Intracellular Fluid/metabolism , Male , Nodose Ganglion/cytology , Nodose Ganglion/drug effects , Nodose Ganglion/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Cholecystokinin A , Receptor, Cholecystokinin B , Receptors, Cholecystokinin/antagonists & inhibitors , Receptors, Cholecystokinin/metabolism , Sincalide/pharmacology , Time Factors
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