title: beta(2)-Adrenoceptor-mediated facilitation of glutamatergic transmission in rat ventromedial hypothalamic neurons.
abstract: Adrenergic modulation of glutamatergic spontaneous miniature excitatory postsynaptic currents (mEPSCs) was investigated in mechanically dissociated rat ventromedial hypothalamic (VMH) neurons using a conventional whole-cell patch clamp technique. Noradrenaline (NA) reversibly increased mEPSC frequency without affecting the current amplitude in a concentration-dependent manner, indicating that NA acts presynaptically to facilitate the probability of spontaneous glutamate release. NA (10 microM) action on glutamatergic mEPSC frequency was completely blocked by 1 microM ICI-188551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methyl-ethyl)amino]-2-butanol], a selective beta(2)-adrenoceptor antagonist, and mimicked by 1 microM formoterol, a selective beta(2)-adrenoceptor agonist. Neither alpha-adrenoceptor nor beta(1)-adrenoceptor blockers affected the NA-induced increase in mEPSC frequency. NA action on glutamatergic mEPSC frequency was completely occluded in the presence of either 10 microM forskolin, an adenylyl cyclase (AC) activator, or blocked by 1 microM SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine], a selective AC inhibitor. Furthermore, the NA-induced increase in mEPSC frequency was completely attenuated by either 1 muM KT5720 or 1 microM H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), specific PKA inhibitors. However, NA still could increase mEPSC frequency either in the Ca(2+)-free external solution or in the presence of 1 microM thapsigargin. The results suggest that activation of presynaptic beta(2)-adrenoceptors facilitates spontaneous glutamate release to VMH neurons via cAMP/PKA signal transduction pathway. beta(2)-Adrenoceptor-mediated presynaptic modulation of excitatory glutamatergic transmission would therefore be expected to play a pivotal role in the regulation of a variety of behavioral functions, which are mediated by the VMH.
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, 188-1 Samduk 2 ga-dong, Jung-gu, Daegu 700-412, Republic of Korea.
authors.forename: J-G
authors.initials: JG
authors.lastname: Lee
authors.forename: I-S
authors.initials: IS
authors.lastname: Choi
authors.forename: E-J
authors.initials: EJ
authors.lastname: Park
authors.forename: J-H
authors.initials: JH
authors.lastname: Cho
authors.forename: M-G
authors.initials: MG
authors.lastname: Lee
authors.forename: B-J
authors.initials: BJ
authors.lastname: Choi
authors.forename: I-S
authors.initials: IS
authors.lastname: Jang
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D018343:Receptors, Adrenergic, beta-2; D018698:Glutamic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine