Modulation of Recombinant GABA Receptor/Channel Subunits by Domain-specific Antibodies in Xenopus Oocytes

Ekema, George; Zheng, Wei; Wang, L.; Lü, Lili

doi:10.1007/s00232-001-0068-3

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…Antibodies raised against the N-terminal domain of ρ1 GABA C receptor protein have been shown to antagonise ρ1 GABA C receptors expressed in oocytes [84].…”

Section: Gaba C Receptor Antagonistsmentioning

confidence: 99%

GABAC Receptors as Drug Targets

Johnston¹,

Chebib²,

Hanrahan³

et al. 2003

CDTCNSND

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GABA(C) receptors are the least studied of the three major classes of GABA receptors. The physiological roles of GABA(C) receptors are still being unravelled and the pharmacology of these receptors is being developed. A range of agents has been described that act on GABA(C) receptors with varying degrees of specificity as agonists, partial agonists, antagonists and allosteric modulators. Pharmacological differences are known to exist between subtypes of cloned GABA(C) receptors that have been cloned from mammalian sources. There is evidence for functional GABA(C) receptors in the retina, spinal cord, superior colliculus, pituitary and gastrointestinal tract. Given the lower abundance and less widespread distribution of GABA(C) receptors in the CNS compared to GABA(A) receptors, GABA(C) receptors may be a more selective drug target than GABA(A) receptors. The major indications for drugs acting on GABA(C) receptors are in the treatment of visual, sleep and cognitive disorders. The most promising leads are THIP, a GABA(C) receptor antagonist in addition to its well known activity as a GABA(A) receptor partial agonist, which is being evaluated for sleep therapy, and CGP36742, an orally active GABA(B) and GABA(C) receptor antagonist, which enhances cognition. Analogues of THIP and CGP36742, such as aza-THIP, that are selective for GABA(C) receptors are being developed. TPMPA and related compounds such as P4MPA, PPA and SEPI are also important leads for the development of systemically active selective GABA(C) receptor antagonists.

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“…Antibodies raised against the N-terminal domain of ρ1 GABA C receptor protein have been shown to antagonise ρ1 GABA C receptors expressed in oocytes [84].…”

Section: Gaba C Receptor Antagonistsmentioning

confidence: 99%

GABAC Receptors as Drug Targets

Johnston¹,

Chebib²,

Hanrahan³

et al. 2003

CDTCNSND

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“…3A,B) could reflect antibody binding to only a minor fraction of the overall receptor population. A previous study describing an antibody raised against the N -terminal half of recombinant ρ1 subunit reported an inhibitory effect on GABA-elicited responses in ρ1 GABA C -expressing oocytes (Ekema et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

Subunit-specific polyclonal antibody targeting human ρ1 GABAC receptor

Gussin

Khasawneh

Xie

et al. 2011

Experimental Eye Research

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The GABAC receptor, a postsynaptic membrane receptor expressed prominently in the retina, is a ligand-gated ion channel that consists of a combination of ρ subunits. We report characterization of a novel guinea pig polyclonal antibody, termed GABAC Ab N-14, directed against a 14-mer peptide (N-14) of the extracellular domain of the human ρ1 subunit. The antibody exhibits high sensitivity for N-14 by ELISA. In Western blots, GABAC Ab N-14 shows reactivity with the ρ1 subunit of preparations obtained from ρ1 GABAC-expressing neuroblastoma cells, Xenopus oocytes, and mammalian retina and brain. Flow cytometry reveals a rightward shift in mean fluorescence intensity of GABAC-expressing neuroblastoma cells probed with GABAC Ab N-14. Immunostaining of neuroblastoma cells and oocytes with GABAC Ab N-14 yields fluorescence only with GABAC-expressing cells. Antibody binding has no effect on GABA-elicited membrane current responses. Immunostaining of human retinal sections shows preferential staining within the inner plexiform layer. GABAC Ab N-14 appears well suited for investigative studies of GABAC ρ1 subunit in retina and other neural tissues.

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“…This further test may also be performed, but it should be noted that the actions of both may not always be identical due to different target sites, e.g. binding of GABA receptor subunit antibodies to extracellular sequences may activate the receptors with a significantly reduced rate of desensitisation to that observed with GABA (Ekema et al, 2001). However, this may be particularly useful The effect of the antibody is cell type specific.…”

Section: Control Procedures-suggested Criteria To Determine Antibody mentioning

confidence: 92%

“…Antibodies may assist with such identification since they are able to modulate the function of GABA receptors. In the absence of GABA, antibodies to the extracellular N-terminus of ␤2, ␥2 or 1 subunits could evoke currents when perfused onto Xenopus oocytes expressing the relevant subunits (Ekema et al, 2001). The current evoked by these antibodies could be equal to that of GABA (anti-1) or indeed several-fold greater (anti-␤2 or -␥2).…”

Section: Gaba Receptorsmentioning

confidence: 99%