title: Leptin influences the excitability of area postrema neurons.
abstract: The area postrema (AP) is a circumventricular organ with important roles in central autonomic regulation. This medullary structure has been shown to express the leptin receptor and has been suggested to have a role in modulating peripheral signals, indicating energy status. Using RT-PCR, we have confirmed the presence of mRNA for the leptin receptor, ObRb, in AP, and whole cell current-clamp recordings from dissociated AP neurons demonstrated that leptin influenced the excitability of 51% (42/82) of AP neurons. The majority of responsive neurons (62%) exhibited a depolarization (5.3 ± 0.7 mV), while the remaining affected cells (16/42) demonstrated hyperpolarizing effects (-5.96 ± 0.95 mV). Amylin was found to influence the same population of AP neurons. To elucidate the mechanism(s) of leptin and amylin actions in the AP, we used fluorescence resonance energy transfer (FRET) to determine the effect of these peptides on cAMP levels in single AP neurons. Leptin and amylin were found to elevate cAMP levels in the same dissociated AP neurons (leptin: % total FRET response 25.3 ± 4.9, n = 14; amylin: % total FRET response 21.7 ± 3.1, n = 13). When leptin and amylin were coapplied, % total FRET response rose to 53.0 ± 8.3 (n = 6). The demonstration that leptin and amylin influence a subpopulation of AP neurons and that these two signaling molecules have additive effects on single AP neurons to increase cAMP, supports a role for the AP as a central nervous system location at which these circulating signals may act through common intracellular signaling pathways to influence central control of energy balance.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Smith
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Paulina
authors.initials: P
authors.lastname: Brzezinska
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Fabien
authors.initials: F
authors.lastname: Hubert
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mimee
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Donald H
authors.initials: DH
authors.lastname: Maurice
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada avf@queensu.ca.
authors.forename: Alastair V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D000200:Action Potentials; D000818:Animals; D031608:Area Postrema / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D013997:Time Factors
chemical_list: D058228:Islet Amyloid Polypeptide; D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; D000242:Cyclic AMP
keywords: amylin; cAMP; caudal brain stem; circumventricular organ; energy balance; obesity