title: Electrophysiologically identified presynaptic mechanisms underlying amylinergic modulation of area postrema neuronal excitability in rat brain slices.
abstract: Amylin, which is co-secreted together with insulin by pancreatic beta cells, is considered to be an important peptide hormone involved in the control of feeding behavior and energy homeostasis. Although the area postrema has been implicated to be a primary target of amylin, there are no studies of the mechanisms by which amylin may alter the excitability of area postrema neurons. To investigate the mechanism for amylinergic modulation of neuronal excitability, we performed perforated patch-clamp recordings from area postrema neurons in rat brainstem slices. Amylin-induced changes in excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents) and changes in the amplitude distribution of mEPSCs, were found in cells not displaying the hyperpolarization-activated cation current (I(h)). Area postrema cells displaying I(h) did not respond to amylin application. Inhibitory responses to amylin were never encountered. Bath application of CNQX (AMPA type glutamate receptor antagonist) abolished the effects of amylin. Depolarization of cells during amylin application was sufficient at 1 μM to cause action potential discharge by responding cells. We conclude that amylin receptors are located mostly on presynaptic glutamatergic terminals connecting to the area postrema neurons not displaying I(h) and amylin concentrations can increase glutamate release enough to cause cell firing. Modulation of amylinergic activity may offer a novel target to influence food intake and obesity.
authors.affiliation: Department of Oral Diagnosis and Medicine, Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo 060-8586, Japan. fkd@den.hokudai.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hirai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Maezawa
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Funahashi
mesh_terms: D000818:Animals; D031608:Area Postrema / Q000166:cytology / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D058228:Islet Amyloid Polypeptide; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D018698:Glutamic Acid