Presynaptic GABAB and adenosine A1 receptors regulate synaptic transmission to rat substantia nigra reticulata neurones.
1. Patch pipettes were used to record whole-cell currents under voltage clamp in substantia nigra zona reticulata (SNR) neurones in the rat midbrain slice. Bipolar electrodes evoked synaptic currents mediated by glutamate (EPSCs) and GABAA receptors (IPSCs). 2. Baclofen reduced the amplitude of IPSCs by 48% at its IC50 value of 0.60 microM. The GABAB antagonist CGP 35348 blocked this effect with a Kd value estimated by Schild analysis of 5 microM. 3. Adenosine reduced IPSCs by 48% at its IC50 value of 56 microM. Adenosine agonists reduced IPSCs with the following rank order of potency: CPA (N6-cyclopentyladenosine) > R-PIA (R(-)N6-(2-phenylisopropyl)adenosine) > CHA (N6-cyclohexyladenosine) = NECA (5'-N-ethylcarboxamidoadenosine) > 2-CADO (2-chloroadenosine) > adenosine. Schild analysis yielded a Kd value of 0.4 nM for antagonism of CPA by the adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine). 4. Both baclofen and adenosine reduced the magnitude of paired-pulse depression of IPSCs, and neither blocked currents evoked by GABA, which was pressure-ejected from micropipettes. 5. Glutamate EPSCs were reduced by baclofen (IC50 = 0.78 microM) and adenosine (IC50 = 57 microM). Schild analysis yielded a Kd value of 11 microM for antagonism of baclofen-induced inhibition of EPSCs by CGP 35348. DPCPX (1 microM) completely blocked the inhibitory effects of adenosine (100 microM) and CPA (100 nM) on EPSCs. Neither adenosine nor baclofen reduced inward currents evoked by glutamate which was pressure-ejected from micropipettes. 6. These results show that presynaptic GABAB and A1 receptors reduce glutamate and GABA release from nerve terminals in the SNR.
Shen
K Z
KZ
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201, USA.
Johnson
S W
SW
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D018047:Receptors, Purinergic P1; D014970:Xanthines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; C051360:1,3-dipropyl-8-cyclopentylxanthine; D001418:Baclofen; D000241:Adenosine