Cholecystokinin increases cytosolic calcium in a subpopulation of cultured vagal afferent neurons.
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.
Simasko
Steven M
SM
Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164, USA. simasko@vetmed.wsu.edu
Wiens
Jason
J
Karpiel
Adrienne
A
Covasa
Mihai
M
Ritter
Robert C
RC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002766:Cholecystokinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058451:JMV 180; D002766:Cholecystokinin; D012844:Sincalide; D002118:Calcium; D016257:Fura-2