Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.8 (FAST)
 758 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FAST and SLOW selected mouse lines were bred for differences in locomotor response to low-dose ethanol. FAST mice exhibit an extreme stimulant response and SLOW mice exhibit locomotor depression at the same ethanol dose. We tested the hypothesis that gamma-aminobutyric acid (GABA) systems modulate ethanol's stimulant effects by examining convulsant responses to GABAA receptor ligands, and by assessing the effects of GABAA and GABAB ligands on locomotor activity in the presence and absence of EtOH. FAST mice were more sensitive to the convulsant effects of GABAA drugs, and to one of two non-GABAergic drugs also tested. FAST and SLOW mice differed in locomotor responses to two benzodiazepines, but not to other GABAA receptor ligands. Ethanol's stimulant effects were not selectively altered by bicuculline or picrotoxin. The selected lines differed in sensitivity to the locomotor depressant effects of the GABAB agonist, baclofen. Ethanol-stimulated activity of FAST mice was inhibited by baclofen, and this effect was reversed by administration of the GABAB antagonist, CGP-35348. These GABAB receptor mediated effects were replicated in DBA/2J inbred mice that exhibit extreme sensitivity to ethanol's stimulant effects. In summary, we found moderate to strong evidence that some sites on the GABAA receptor complex were altered as a consequence of selection of FAST and SLOW mice, but found little support for GABAA mediation of EtOH-stimulated activity. In contrast, we found moderate evidence for differential alteration of GABAB receptor function; however, GABAB receptor involvement in ethanol-stimulated activity was strongly supported by results in the selected lines and an inbred strain.
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PMID:Seizure sensitivity and GABAergic modulation of ethanol sensitivity in selectively bred FAST and SLOW mouse lines. 980 87

Mice selectively bred for high (FAST) or low (SLOW) locomotor stimulant response to ethanol have been found to differ in response to drugs with gamma-aminobutyric acid (GABA)-ergic actions. Reverse selection produced lines that are similar in sensitivity to ethanol stimulation (r-FAST and r-SLOW) and provided a unique model for testing hypotheses about shared genetic influence on sensitivity to ethanol and GABAergic drugs. FAST mice were more stimulated than SLOW mice by all drugs tested: ethanol, methanol, n-propanol, t-butanol, pentobarbital, diazepam, and allopregnanolone. In contrast, r-FAST and r-SLOW mice differed in sensitivity to only a few isolated drug doses. Locomotor responses of each reverse-selected line were significantly different from the responses of their respective forward-selected line for all drugs. Results support an effect of selection for ethanol sensitivity on allosteric modulation of the GABA-A receptor.
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PMID:Locomotor activity responses to ethanol, other alcohols, and GABA-A acting compounds in forward- and reverse-selected FAST and SLOW mouse lines. 1249 94

The physiological and pharmacological properties of gamma-aminobutyric acid (GABA)ergic miniature inhibitory postsynaptic currents (mIPSCs) were investigated in substantia gelatinosa neurons of mouse spinal cord using whole-cell patch clamp recordings. Two cell populations were pharmacologically identified based on the effect of propofol (10 muM) on the mIPSC decay kinetics: those exhibiting propofol-sensitive mIPSCs, with a slow decay kinetic (mIPSC(SLOW)), and those exhibiting propofol-resistant mIPSCs, with a fast decay kinetic (mIPSC(FAST)) (decay time constants of 14.2+/-0.7 and 7.4+/-0.8 ms, respectively). The frequency and amplitude of both types of mIPSCs were not affected by propofol. Miniature IPSC(FAST) showed midazolam insensitivity, while midazolam prolonged the decay phase of mIPSC(SLOW) without modulation of the frequency and amplitude. Exogenous GABA-evoked responses in the neurons with mIPSC(SLOW) were potentiated by propofol, while those in neurons with mIPSC(FAST) were unaffected by propofol. Furthermore, non-stationary noise analysis of the two kinetically and pharmacologically distinct mIPSCs revealed different conductance of GABA(A) receptor channels underlying the synaptic events. Pharmacological responses to propofol and midazolam suggested that mIPSC(FAST) and mIPSC(SLOW) in substantia gelatinosa neurons can be mediated by GABA(A) receptors with different subunit compositions.
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PMID:Two types of GABAergic miniature inhibitory postsynaptic currents in mouse substantia gelatinosa neurons. 1706 85