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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.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Lee JG,Choi IS,Park EJ,Cho JH,Lee MG,Choi BJ,Jang IS

doi

10.1016/j.neuroscience.2006.10.049

subject

Has Abstract

pub_date

2007-02-23 00:00:00

pages

1255-65

issue

4

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(06)01471-0

journal_volume

144

pub_type

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