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trans ‐4‐Amino‐2‐methylbut‐2‐enoic acid (2‐MeTACA) and (±)‐ trans ‐2‐aminomethylcyclopropanecarboxylic acid ((±)‐TAMP) can differentiate rat ρ3 from human ρ1 and ρ2 recombinant GABA C receptors
This study investigated the effects of a number of GABA analogues on rat ρ3 GABA C receptors expressed in Xenopus oocytes using 2‐electrode voltage clamp methods. The potency order of agonists was muscimol (EC 50 =1.9±0.1 μ M ) (+)‐ trans ‐3‐aminocyclopentanecarboxylic acids ((+)‐TACP; EC 50 =2.7±0....
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| Published in: | British journal of pharmacology 2009-02, Vol.135 (4), p.883-890 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
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| Online Access: | Get full text |
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| Summary: | This study investigated the effects of a number of GABA analogues on rat ρ3 GABA
C
receptors expressed in
Xenopus
oocytes using 2‐electrode voltage clamp methods.
The potency order of agonists was muscimol (EC
50
=1.9±0.1 μ
M
) (+)‐
trans
‐3‐aminocyclopentanecarboxylic acids ((+)‐TACP; EC
50
=2.7±0.9 μ
M
) trans‐4‐aminocrotonic acid (TACA; EC
50
=3.8±0.3 μ
M
) GABA (EC
50
=4.0±0.3 μ
M
) > thiomuscimol (EC
50
=24.8±2.6 μ
M
) > (±)‐
cis
‐2‐aminomethylcyclopropane‐carboxylic acid ((±)‐CAMP; EC
50
=52.6±8.7 μ
M
) >
cis
‐4‐aminocrotonic acid (CACA; EC
50
=139.4±5.2 μ
M
).
The potency order of antagonists was (±)‐
trans
‐2‐aminomethylcyclopropanecarboxylic acid ((±)‐TAMP;
K
B
=4.8±1.8 μ
M
) (1,2,5,6‐tetrahydropyridin‐4‐yl)methylphosphinic acid (TPMPA;
K
B
=4.8±0.8 μ
M
) > (piperidin‐4‐yl)methylphosphinic acid (P4MPA;
K
B
=10.2±2.3 μ
M
) 4,5,6,7‐tetrahydroisoxazolo[5,4‐
c
]pyridin‐3‐ol (THIP;
K
B
=10.2±0.3 μ
M
) imidazole‐4‐acetic acid (I4AA;
K
B
=12.6±2.7 μ
M
) > 3‐aminopropylphosphonic acid (3‐APA;
K
B
=35.8±13.5 μ
M
).
trans
‐4‐Amino‐2‐methylbut‐2‐enoic acid (2‐MeTACA; 300 μ
M
) had no effect as an agonist or an antagonist indicating that the C2 methyl substituent is sterically interacting with the ligand‐binding site of rat ρ3 GABA
C
receptors.
2‐MeTACA affects ρ1 and ρ2 but not ρ3 GABA
C
receptors. In contrast, (±)‐TAMP is a partial agonist at ρ1 and ρ2 GABA
C
receptors, while at rat ρ3 GABA
C
receptors it is an antagonist. Thus, 2‐MeTACA and (±)‐TAMP could be important pharmacological tools because they may functionally differentiate between ρ1, ρ2 and ρ3 GABA
C
receptors
in vitro
.
British Journal of Pharmacology
(2002)
135
, 883–890; doi:
10.1038/sj.bjp.0704432 |
|---|---|
| ISSN: | 0007-1188 1476-5381 |
| DOI: | 10.1038/sj.bjp.0704432 |