Cholecystokinin Octapeptide Increases Spontaneous Glutamatergic Synaptic Transmission to Neurons of the Nucleus Tractus Solitarius Centralis

• Published in: Journal of neurophysiology 2005-10, Vol.94 (4), p.2763-2771
• Main Authors: Baptista, V, Zheng, Z. L, Coleman, F. H, Rogers, R. C, Travagli, R. A
• Format: Article
• Language: English
• Subjects: Anesthetics, Local - pharmacology; Animals; Animals, Newborn; Bicuculline - pharmacology; Biotin - analogs & derivatives; Biotin - metabolism; Dose-Response Relationship, Drug; Drug Interactions; Excitatory Postsynaptic Potentials - drug effects; Female; GABA Antagonists - pharmacology; Glutamic Acid - metabolism; Hormone Antagonists - pharmacology; Imaging, Three-Dimensional - methods; Immunohistochemistry - methods; In Vitro Techniques; Male; Neural Inhibition - drug effects; Neurons - drug effects; Neurons - metabolism; Patch-Clamp Techniques - methods; Peptides - pharmacology; Proglumide - analogs & derivatives; Proglumide - pharmacology; Rats; Rats, Sprague-Dawley; Sincalide - pharmacology; Solitary Nucleus - cytology; Solitary Nucleus - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tetrodotoxin - pharmacology; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00351.2005

Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana Submitted 4 April 2005; accepted in final form 15 June 2005 Cholecystokinin (CCK) is released from enteroendocrine cells after ingestion of nutrients and induces multiple effects along the gastrointestinal tract, including gastric relaxation and short-term satiety. We used whole cell patch-clamp and immunohistochemical techniques in rat brain stem slices to characterize the effects of CCK. In 45% of the neurons of nucleus tractus solitarius subnucleus centralis (cNTS), perfusion with the sulfated form of CCK (CCK-8s) increased the frequency of spontaneous excitatory currents (sEPSCs) in a concentration-dependent manner (1–300 nM). The threshold for the CCK-8s excitatory effect was 1 nM, the EC 50 was 20 nM, and E max was 100 nM. The excitatory effects of CCK-8s were still present when the slices were preincubated with tetrodotoxin or bicuculline or when the recordings were conducted with Cs + electrodes. Pretreatment with the CCK-A receptor antagonist, lorglumide (1 µM), antagonized the effects of CCK-8s, whereas perfusion with the CCK-B preferring agonist CCK-8 nonsulfated (CCK-ns, 1 µM) did not affect the frequency of sEPSCs. Similarly, pretreatment with the CCK-B receptor antagonist, triglumide (1 µM), did not prevent the actions of CCK-8s. Although the majority (i.e., 76%) of CCK-8s unresponsive cNTS neurons had a bipolar somata shape and were TH-IR negative, no differences were found in either the morphological or the neurochemical phenotype of cNTS neurons responsive to CCK-8s. Our results suggest that the excitatory effects of CCK-8s on terminals impinging on a subpopulation of cNTS neurons are mediated by CCK-A receptors; these responsive neurons, however, do not have morphological or neurochemical characteristics that automatically distinguish them from nonresponsive neurons. Address for reprint requests and other correspondence: R. A. Travagli, Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808 (E-mail: Alberto.Travagli{at}pbrc.edu )