title: Cholecystokinin and neurotensin inversely modulate excitatory synaptic transmission in the parabrachial nucleus in vitro.
abstract: Cholecystokinin and neurotensin are present in fibres innervating the parabrachial nucleus and have previously been shown to modulate the flow of visceral afferent information through the parabrachial nucleus to the cortex in the rat. This study examined the effects of cholecystokinin and neurotensin on synaptic transmission in the parabrachial nucleus using a pontine slice preparation and the nystatin perforated-patch recording technique. Stimulation of the ventral, external lateral portion of the parabrachial nucleus elicited glutamate-mediated, excitatory postsynaptic currents in cells recorded in the parabrachial nucleus. Bath application of neurotensin dose-dependently and reversibly enhanced, while cholecystokinin attenuated, the evoked excitatory postsynaptic current. In addition, the frequency of spontaneous, miniature excitatory postsynaptic currents recorded in parabrachial nucleus cells was significantly increased by neurotensin and decreased by cholecystokinin application. Paired-pulse depression was also enhanced and decreased by neurotensin and cholecystokinin, respectively. These synaptic changes induced by neurotensin and cholecystokinin were not accompanied by changes in input resistance of parabrachial nucleus cells over a wide voltage range (although neurotensin reduced an outwardly rectifying conductance at potentials positive to -20 mV), nor did these peptides alter the inward current induced by a brief bath application of the glutamate agonist, alpha-amino-3-hydroxy-methylisoxazole-4-propionate. The neurotensin antagonist, SR48692 (100 microM), completely and reversibly blocked the neurotensin-induced enhancement of the excitatory postsynaptic current. The non-selective cholecystokinin receptor antagonist, proglumide (100 microM), completely and reversibly blocked the cholecystokinin-induced attenuation of the excitatory postsynaptic current. In addition, the selective cholecystokinin-A receptor antagonist, L-364,718 (10 microM), but not the selective cholecystokinin-B receptor antagonist, L-365,260 (100 microM), blocked the effect of cholecystokinin on synaptic transmission. These results suggest that neurotensin and cholecystokinin act at presynaptic neurotensin and cholecystokinin-A receptors, respectively, to modulate excitatory synaptic transmission in the parabrachial nucleus.
authors.affiliation: Neuroscience Research Group, University of Calgary, Alberta, Canada.
authors.forename: T M
authors.initials: TM
authors.lastname: Saleh
authors.forename: S B
authors.initials: SB
authors.lastname: Kombian
authors.forename: J A
authors.initials: JA
authors.lastname: Zidichouski
authors.forename: Q J
authors.initials: QJ
authors.lastname: Pittman
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000737:chemistry / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D009475:Neurons, Afferent / Q000737:chemistry / Q000502:physiology; D009496:Neurotensin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010671:Phenylurea Compounds; D011149:Pons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000502:physiology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D001570:Benzodiazepinones; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; D011720:Pyrazoles; D011804:Quinolines; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D018028:Receptors, Neurotensin; D001569:Benzodiazepines; C079087:SR 48692; C079692:GYKI 53655; C058121:L 365260; D009496:Neurotensin; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002766:Cholecystokinin; D020109:Devazepide