title: In vitro analysis of the effects of cholecystokinin on rat brain stem motoneurons.
abstract: Using whole cell patch clamp in thin brain stem slices, we tested the effects of cholecystokinin (CCK) on identified gastric-projecting neurons of the rat dorsal motor nucleus of the vagus (DMV). Perfusion with the sulfated form of CCK octapeptide (CCK8s, 30 pM-300 nM, EC50 approximately 4 nM) induced a concentration-dependent inward current in 35 and 41% of corpus- and antrum/pylorus-projecting DMV neurons, respectively. Conversely, none of the fundus-projecting DMV neurons responded to perfusion with CCK8s. The CCK8s-induced inward current was accompanied by a 65 +/- 17% increase in membrane input resistance and reversed at 90 +/- 4 mV, indicating that the excitatory effects of CCK8s were mediated by the closure of a potassium conductance. Pretreatment with the synaptic blocker TTX (0.3-1 microM) reduced the CCK8s-induced current, suggesting that a portion of the CCK8s-induced current was mediated indirectly via an action on presynaptic neurons apposing the DMV membrane. Pretreatment with the selective CCK-A receptor antagonist lorglumide (0.3-3 microM) attenuated the CCK8s-induced inward current in a concentration-dependent manner, with a maximum inhibition of 69 +/- 12% obtained with 3 microM lorglumide. Conversely, pretreatment with the selective CCK-B antagonist triglumide did not attenuate the CCK8s-induced inward current; pretreatment with triglumide (3 microM) and lorglumide (1 microM) attenuated the CCK8s-induced current to the same extent as pretreatment with lorglumide alone. Immunohistochemical experiments showed that CCK-A receptors were localized on the membrane of 34, 65, and 60% of fundus-, corpus-, and antrum/pylorus-projecting DMV neurons, respectively. Our data indicate that CCK-A receptors are present on a subpopulation of gastric-projecting neurons and that their activation leads to excitation of the DMV membrane.
authors.affiliation: Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Rd., Baton Rouge, Louisiana 70808, USA.
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Zheng
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lewis
authors.forename: R Alberto
authors.initials: RA
authors.lastname: Travagli
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000502:physiology*; D002766:Cholecystokinin / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000502:physiology; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000502:physiology; D013270:Stomach / Q000294:innervation
chemical_list: D010446:Peptide Fragments; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; C410885:cholecystokinin 8; D002766:Cholecystokinin