A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system

Pertussis Toxin Lesions of the Rat Substantia Nigra Block the Inhibitory Effects of the γ-Hydroxybutyrate Agent, S(-)HA-966 without Affecting the Basal Firing Properties of Dopamine Neurons

“…As a member of the large family of G protein-coupled receptors, postsynaptic GABA B receptors are known to be inactivated by PT (Reisine 1990;Misgeld et al 1995). The results of the present study are entirely consistent with previous pharmacological data implicating these receptors in the inhibitory effects of S(-)HA-966.…”

“…Sensitivity to PT is widely regarded as presumptive evidence that a response is mediated via G protein-coupled receptors (Reisine 1990;Misgeld et al 1995). The toxin acts by ADP-ribosylating a cysteine residue on the ␣ subunit of G i/o , uncoupling the receptor from its effector.…”

“…Although GABA B receptors couple to a variety of transduction mechanisms, their inhibitory postsynaptic effects are mediated primarily by activation of an inwardly rectifying K ϩ channel (Newberry and Nicoll 1984;Gähwiler and Brown 1985;Misgeld et al 1995;Lüscher et al 1997). Unlike their ionotropic counterparts, metabotropic GABA B receptors exert their effects indirectly through activation of the guanine nucleotide binding proteins, G 0 and G i (Andrade et al 1986;Thompson and Gähwiler 1992).…”

“…Unlike their ionotropic counterparts, metabotropic GABA B receptors exert their effects indirectly through activation of the guanine nucleotide binding proteins, G 0 and G i (Andrade et al 1986;Thompson and Gähwiler 1992). Pertussis toxin (PT), a compound that inactivates G i/o proteins via ADP-ribosylation, blocks the postsynaptic actions of the GABA B agonist baclofen on a variety of neurons (reviewed by Reisine 1990;Misgeld et al 1995). PT has also been shown to prevent absence seizures induced by GHB, an effect that has been attributed to an increase in a GABA B receptor-mediated K ϩ conductance in thalamocortical neurons (Williams et al 1995).…”

Activation of Postsynaptic GABABReceptors Modulates the Bursting Pattern and Synaptic Activity of Olfactory Bulb Juxtaglomerular Neurons

“…In particular, GABA B -Rs may modulate calcium channels, which were recently shown to be located mostly on the distal dendrites of ET cells (Zhou et al 2006). Activation of presynaptic GABA B -Rs reduces neurotransmitter release at many central synapses (Chen and Pan 2006;Misgeld et al 1995). For instance, baclofen decreases GABA and glutamate release in hypothalamic paraventricular neurons (Cui et al 2000;Wang et al 2003).…”