title: Vanilloid, purinergic, and CCK receptors activate glutamate release on single neurons of the nucleus tractus solitarius centralis.
abstract: Baroreceptor inputs to nucleus of the tractus solitarius medialis (mNTS) neurons can be differentiated, among other features, by their response to vanilloid or purinergic agonists, active only on C- or A-fibers, respectively. A major aim of this study was to examine whether neurons of NTS centralis (cNTS), a subnucleus dominated by esophageal inputs, exhibit a similar dichotomy. Since it has been suggested that cholecystokinin (CCK), exerts its gastrointestinal (GI)-related effects via paracrine activation of vagal afferent C-fibers, we tested whether CCK-sensitive fibers impinging upon cNTS neurons are responsive to vanilloid but not purinergic agonists. Using whole cell patch-clamp recordings from cNTS, we recorded miniature excitatory postsynaptic currents (mEPSCs) to test the effects of the vanilloid agonist capsaicin, the purinergic agonist α,β-methylene-ATP (α,β-Met-ATP), and/or CCK-octapeptide (CCK-8s). α,β-Met-ATP, capsaicin; and CCK-8s increased EPSC frequency in 37, 71, and 46% of cNTS neurons, respectively. Approximately 30% of cNTS neurons were responsive to both CCK-8s and α,β-Met-ATP, to CCK-8s and capsaicin, or to α,β-Met-ATP and capsaicin, while 32% of neurons were responsive to all three agonists. All neurons responding to either α,β-Met-ATP or CCK-8s were also responsive to capsaicin. Perivagal capsaicin, which is supposed to induce a selective degeneration of C-fibers, decreased the number of cNTS neurons responding to capsaicin or CCK-8s but not those responding to α,β-Met-ATP. In summary, GI inputs to cNTS neurons cannot be distinguished on the basis of their selective responses to α,β-Met-ATP or capsaicin. Our data also indicate that CCK-8s increases glutamate release from purinergic and vanilloid responsive fibers impinging on cNTS neurons.
authors.affiliation: Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania 17033-0850, USA.
authors.forename: Kirsteen N
authors.initials: KN
authors.lastname: Browning
authors.forename: Shuxia
authors.initials: S
authors.lastname: Wan
authors.forename: Vander
authors.initials: V
authors.lastname: Baptista
authors.forename: R Alberto
authors.initials: RA
authors.lastname: Travagli
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D017552:Solitary Nucleus / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; D011983:Receptors, Purinergic; D050916:TRPV Cation Channels; C410885:cholecystokinin 8; D018698:Glutamic Acid; D002766:Cholecystokinin; D002211:Capsaicin