Presynaptic GABAB receptor activation attenuates synaptic transmission to rat sympathetic preganglionic neurons in vitro.
Intracellular recordings were made from sympathetic preganglionic neurons (SPNs) in transverse neonate rat spinal cord slices. Superfusion of gamma-aminobutyric acid (GABA; 25-100 microM) or (-)-baclofen (1-30 microM) consistently attenuated the excitatory postsynaptic potentials (EPSPs) evoked by stimulation of dorsal rootlets or lateral funiculus, without causing a significant change of the resting membrane potential and input resistance of the SPNs or of the depolarizations induced by pressure applications of glutamate; the IC50 for baclofen was 2.5 microM. When superfused at a higher concentration (greater than or equal to 500 microM) or ejected by pressure GABA caused a bicuculline-sensitive membrane hyperpolarization. The enantiomer (+)-baclofen (10-50 microM) and the GABAA agonist muscimol (1-10 microM) had no significant effect on the EPSPs. The GABAB receptor antagonist 2-hydroxy-saclofen caused a 10 fold rightward shift of the baclofen dose-response curve, whereas the GABAA receptor antagonist bicuculline (10-50 microM) was ineffective. Glycine had no significant effects on the EPSPs in the concentrations (10-100 microM) tested here. The results indicate that of the two putative inhibitory transmitters in the spinal cord GABA but not glycine depresses EPSPs evoked in the rat SPNs by acting on presynaptic GABAB receptors, the activation of which results in a reduction of excitatory transmitter release.
Department of Anatomy, Medical College of Ohio, Toledo 43699.
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D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects*; D001418:Baclofen / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005971:Glutamates; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen