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Chemical Compound Review:

AG-D-93483 benzyl-[3-[1-(3,4- dichlorophenyl)ethylamin...

Synonyms: SureCN2947846, ACMC-20n5cm, CGP-55845, Cgp-55845A, AC1L3XHD, ...

Hasuo, H. et al., Ghorbel, M.T. et al., Kantrowitz, J.T. et al., Giorgetti, M. et al., Jiang, L. et al., et al.

Onali, Olianas,

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High impact information on CGP 55845A

8. The GABAB receptor antagonist CGP 55845A (5 microM) decreased the baseline release probability of inhibitory synapses and attenuated PPD indirectly, rather than by blocking presynaptic GABAB autoreceptors [1].
Further voltage-clamp recordings showed that CGP 55845A increased the duration of the depolarizing GABA component of the GPSC even when the GABA(B) component had already been blocked by internal QX-314, suggesting that CGP 55845A also increased the duration of GABA release [2].
In naive rats, administration of a potent and selective GABA(B) receptor antagonist (CGP 55845A) into the ventral tegmental area elicited a concentration-dependent increase in dopamine levels, but did not alter glutamate levels [3].
The GABA(B) receptor antagonist CGP 55845A competitively counteracted the (-)baclofen potentiation of CRH-stimulated adenylyl cyclase activity with a pA(2) value of 6.70 [4].
When the fast and slow inhibitory postsynaptic potentials were blocked by GABA(A) and GABA(B) receptor antagonists (bicuculline and CGP 55845A respectively), high frequency stimulation produced a large and sustained depolarization followed by long-term potentiation of the excitatory postsynaptic potential [5].

Anatomical context of CGP 55845A

CGP 55845A: a potent antagonist of GABAB receptors in the CA1 region of rat hippocampus [6].
At higher stimulation strength, an approximately 15% reduction of EPSCs occurred in interneurons after paired and primed stimulation, which was not sensitive to CGP 55845A [7].

Associations of CGP 55845A with other chemical compounds

In the VMH, baclofen significantly increased (p < 0.01) mean PRL but SAC and CGP 55845A were ineffective, whereas dialysis of either muscimol or BMI increased mean prolactin (p < 0.01) [8].

Gene context of CGP 55845A

The GABAB receptor antagonists CGP-54626A (1 microM, n = 19), CGP-55845A (1 microM, n = 15), and 2-hydroxysaclofen (0.5 mM, n = 3) attenuated inhibition by baclofen (1-3 microM) but not by muscimol or GABA [9].

Analytical, diagnostic and therapeutic context of CGP 55845A

Here, using microarray technology and RT-PCR of RNA from cultured rat embryonic hippocampal neurones, we report the profile of genes that are up- or downregulated by activation of GABA(B)Rs by baclofen but are not changed by baclofen in the presence of the GABA(B)R antagonist CGP-55845A [10].

References

Paired-pulse modulation at individual GABAergic synapses in rat hippocampus. Jiang, L., Sun, S., Nedergaard, M., Kang, J. J. Physiol. (Lond.) (2000) [Pubmed]
Synaptic depolarizing GABA Response in adults is excitatory and proconvulsive when GABAB receptors are blocked. Kantrowitz, J.T., Francis, N.N., Salah, A., Perkins, K.L. J. Neurophysiol. (2005) [Pubmed]
In vivo modulation of ventral tegmental area dopamine and glutamate efflux by local GABA(B) receptors is altered after repeated amphetamine treatment. Giorgetti, M., Hotsenpiller, G., Froestl, W., Wolf, M.E. Neuroscience (2002) [Pubmed]
Beta gamma-mediated enhancement of corticotropin-releasing hormone-stimulated adenylyl cyclase activity by activation of gamma-aminobutyric acid(B) receptors in membranes of rat frontal cortex. Onali, P., Olianas, M.C. Biochem. Pharmacol. (2001) [Pubmed]
Activation of inhibitory pathways suppresses the induction of long-term potentiation in neurons of the rat lateral septal nucleus. Hasuo, H., Akasu, T. Neuroscience (2001) [Pubmed]
CGP 55845A: a potent antagonist of GABAB receptors in the CA1 region of rat hippocampus. Davies, C.H., Pozza, M.F., Collingridge, G.L. Neuropharmacology (1993) [Pubmed]
Putative cortical and thalamic inputs elicit convergent excitation in a population of GABAergic interneurons of the lateral amygdala. Szinyei, C., Heinbockel, T., Montagne, J., Pape, H.C. J. Neurosci. (2000) [Pubmed]
Effect of infusing gamma-aminobutyric acid receptor agonists and antagonists into the medial preoptic area and ventromedial hypothalamus on prolactin secretion in male sheep. Ferreira, S.A., Browning, D.A., Scott, C.J., Kuehl, D.E., Jackson, G.L. Endocrine (1998) [Pubmed]
Neuronal inhibition by a GABAB receptor agonist in the rostral ventrolateral medulla of the rat. Li, Y.W., Guyenet, P.G. Am. J. Physiol. (1995) [Pubmed]
Profile of changes in gene expression in cultured hippocampal neurones evoked by the GABAB receptor agonist baclofen. Ghorbel, M.T., Becker, K.G., Henley, J.M. Physiol. Genomics (2005) [Pubmed]

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