Mechanisms of action of CCK to activate central vagal afferent terminals.
Cholecystokinin [CCK] is a peptide released as a hormone by the proximal gut in response to the presence of peptones and fatty acid in the gut. Considerable evidence suggests that CCK inhibits feeding behavior and gastric function by acting as a paracrine modulator of vagal afferents in the periphery, especially in the duodenum. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. More recent studies have suggested that CCK may act directly within the CNS to activate central vagal afferent terminal inputs to the solitary nucleus. We have developed an in vitro calcium imaging method that reveals, for the first time, the direct effects of this peptide on vagal terminals in the solitary nucleus. In vitro imaging reveals that CCK provokes increases in intracellular calcium in vagal afferent terminals as a consequence of a complex interaction between protein kinase A [PKA] and phospholipase C [PLC] transduction mechanisms that open L-type calcium channels and causes endoplasmic reticular [ER] calcium release. The subsequent activation of PKC may be responsible for initiating calcium spiking which is dependent on a TTX-sensitive mechanism. Thus, imaging of the isolated but spatially intact hindbrain slice has allowed a more complete appreciation of the interdependent transduction mechanisms used by CCK to excite identified central vagal afferent fibers and varicosities.
Rogers
Richard C
RC
Laboratory of Autonomic Neurosciences, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Richard.Rogers@pbrc.edu
Hermann
Gerlinda E
GE
D000344:Afferent Pathways / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D008297:Male; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000502:physiology; D014630:Vagus Nerve / Q000378:metabolism*
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D002766:Cholecystokinin; D002118:Calcium