GABAb presynaptic

Electrophysiological studies in mammalian CNS suggested subtle distinctions between pre- and postsynaptic GABABRs (see Nicoll 2004 for a review). Stronger evidence that pharmacological differences may exist between GABAb presynaptic... 

In contrast to the metabotropic effects described for presynaptic kainate receptors in CA1 (90,94), the effects of kainate in CA3 appear to be mediated by direct depolarization of the presynaptic terminals. The kainate-induced facilitation is not sensitive to antagonists of other receptors (e.g., GABAb), and can be mimicked by elevating the extracellular potassium concentration (77,100). It has been proposed that the facilitation is owing to increased calcium influx that is induced by modest depolarization of the terminals by kainate receptors, whereas a strong depolarization, in response to activation of a larger receptor population, causes the sodium channels to inactivate and thereby depresses transmission (77,84,88,100-102). 

GABAB baclofen 2-OH saclofen Inhibitory (presynaptic) i Ca2+ conductance Inhibitory (postsynaptic) t K+ conductance... 

Baclofen exerts its spasmolytic activity at GABAb receptors. Activation of these receptors in the brain by baclofen results in hyperpolarization, probably by increased K+ conductance. It has been suggested that hyperpolarization (in the spinal cord as well as in the brain) causes presynaptic inhibition by reducing calcium influx (Figure 27-11) and reduces the release of excitatory transmitters in both the brain and the spinal cord. Baclofen may also reduce pain in patients with spasticity, perhaps by inhibiting the release of substance P in the spinal cord. 

Krueger BK, Font J, Greengard P (1977) Depolarization-induced phosphorylation of specific proteins, mediated by calcium ion influx, in rat brain synaptosomes. J Biol Chem 252 2764-73 Kubista H, Boehm S (2006) Molecular mechanisms underlying the modulation of exocytotic noradrenaline release via presynaptic receptors. Pharmacol Ther 112 213 12 Kulik A, Vida I, Fukazawa Y et al (2006) Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells. J Neurosci 26 4289-97... 

Wu LG, Saggau P (1994) Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus. Neuron 12 1139—48 Wu LG, Saggau P (1995) GABAB receptor-mediated presynaptic inhibition in guinea-pig hippocampus is caused by reduction of presynaptic Ca2+ influx. J Physiol 485 649-57 Wu LG, Saggau P (1997) Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci 20 204—12... 

Is Pharmacological Heterogeneity Limited to Presynaptic GABAb Receptors . .. 398... 

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