<i>CIS</i>‐ AND <i>TRANS</i>‐4‐AMINOCROTONIC ACID AS GABA ANALOGUES OF RESTRICTED CONFORMATION

Johnston, G. A. R.; Curtis, D. R.; Beart, P. M.; Game, C. J. A.; McCulloch, R.M.; Twitchin, B.

doi:10.1111/j.1471-4159.1975.tb07642.x

Cited by 175 publications

(88 citation statements)

References 20 publications

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“…Relative depressant activities of the agonists are listed in Table 1. 4-Amino-3-hydroxybutyric acid (GABOB) and 3-APS (Curtis, H6sli & Johnston, 1968), muscimol, dihydromuscimol, isoguvacine and THIP (Krogsgaard-Larsen, Hjeds, Curtis, Lodge & Johnston, 1979) and trans4-aminocrotonic acid (Johnston, Curtis, Beart, Game, McCulloch & Twitchin, 1975) have the following order of potency as determined by a semiquantitative comparison of depression following electrophoretic application onto cat spinal neurones in vivo: muscimol = dihydromuscimol = 3-APS > isoguvacine > THIP > GABA = trans-4-aminocrotonic acid > GABOB. The depressant values in Table 1, with the exception of GABOB, are in reasonable agreement with this order of depressant potency.…”

Section: Resultsmentioning

confidence: 99%

γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT

Allan

Evans

Johnston

1980

British J Pharmacology

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1Relative molar potencies, of a range of y-aminobutyrate (GABA-related agonists, for depolarization of isolated spinal roots have been compared with their potencies for depression of spontaneous synaptic activity, recorded in ventral roots of hemisected spinal cord preparations from 3 to 9-day-old rats. Both effects were sensitive to antagonism by bicuculline. 2 The depolarizing potencies of the series were not parallelled by their depressant potencies. This disparity was shown most strongly by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) which was 20 times stronger than GABA in depolarizing root fibres and 20 times stronger than GABA in its depressant action and by (+ )cis-3-aminocyclopentane-carboxylic acid (17 times weaker than GABA on root fibres and 42 times stronger than GABA as a depressant). 3 The effect of uptake on these relative potencies is discussed and it is concluded that fibre depolarization and depression are probably mediated by different types of bicuculline-sensitive receptor. 4 The depolarizing potencies of the agonists showed a strong correlation with previously reported data for displacement of labelled GABA from in vitro rat brain membrane preparations (correlation coefficient 0.90, P < 0.001). However, the relative depressant potencies showed no such correlation with binding data (correlation coefficient 0.50, P > 0.05).

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Section: Resultsmentioning

confidence: 99%

γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT

Allan

Evans

Johnston

1980

British J Pharmacology

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“…Bicuculline (50 /SM) antagonized the response to isoguvacine and revealed a small hyperpolarizing response to GABA which was reduced by concomitant application A P3 GABA (100 /M) GABA (300 uM) GABA ( This novel response to GABA resembled that one recorded from fish and rat horizontal and bipolar cells (Qian & Dowling, 1993;Feigenspan et al 1993), from frog optic tectum (Nistri & Sivilotti, 1985), guinea pig superior colliculus (Arakawa & Okada, 1988) or from Xenopus oocytes injected with bovine retinal mRNA (Polenzani, Woodward & Miledi, 1991;Woodward, Polenzani & Miledi, 1993 (Johnston et al 1975;Drew et al 1984). When both bicuculline-sensitive and bicucullinebaclofen-insensitive receptors are expressed together, as in the case of rat retinal bipolar cells (Feigespan et al 1993), CACA has a preferential role for bicuculline and baclofeninsensitive receptors.…”

Section: Methodsmentioning

confidence: 99%

“…A novel type of GABA response, which appears to be mediated through a new type of GABA receptor, termed GABAc, has recently been described in fish and rat retinal horizontal and bipolar cells (Qian & Dowling, 1993;Feigenspan, Wiissle & Bormann, 1993) and in frog and guinea-pig visual pathways (Nistri & Sivilotti, 1985;Arakawa & Okada, 1988). This new receptor type is neither antagonized by bicuculline nor activated by the GABAB agonist baclofen; it is supposed to be selectively activated by the conformationally restricted GABA analogue cis-4-aminocrotonic acid (CACA; Johnston, Curtis, Beart, Game, McCulloch & Twitchin, 1975). In line with these results, bicuculline-insensitive, baclofen-insensitive [3H]GABA binding sites have also been identified in membranes prepared from rat cerebellum (Drew, Johnston & Weatherby, 1984;Drew & Johnston, 1992).…”

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confidence: 99%

Transient expression of a novel type of GABA response in rat CA3 hippocampal neurones during development.

Strata

Cherubini

1994

The Journal of Physiology

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1. Intracellular recordings were used to study the effects of gamma‐aminobutyric acid (GABA) on rat CA3 hippocampal neurones during the first two weeks of postnatal life. 2. In the presence of tetrodotoxin (TTX, 1 microM), from postnatal day 0 (P0) to P12 both associated with an increase in input conductance whereas baclofen (30‐100 microM) produced a membrane hyperpolarization. 3. Bicuculline (50 microM) reduced the effects of GABA and abolished the response to isoguvacine without affecting the response to baclofen. 4. This novel bicuculline‐insensitive GABA response was chloride dependent and was blocked by picrotoxin (10‐100 microM) in an uncompetitive way. In bicuculline and picrotoxin, a GABAB‐mediated hyperpolarization appeared. 5. Towards the end of the second postnatal week, bicuculline blocked the GABA‐induced depolarization and revealed a small hyperpolarizing response which was blocked by the GABAB antagonist CGP 35348 (0.5‐1 mM). 6. It is suggested that, during development, the GABA response was mediated through the conventional GABAA and GABAB receptors as well as a new bicuculline‐baclofen‐insensitive type of receptor.

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“…GABA C responses were first observed in the spinal cord (Johnston et al, 1975), and a "GABA C " binding site was later discovered in the cerebellum that did not bind GABA A or GABA B receptor compounds (Drew et al, 1984). Subsequently, GABA responses attributed to GABA C receptors were obtained when retinal mRNA was expressed in Xenopus oocytes (Polenzani et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Evidence for Inhibition Mediated by Coassembly of GABA_Aand GABA_CReceptor Subunits in Native Central Neurons

Milligan¹,

Buckley²,

Garret³

et al. 2004

J. Neurosci.

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Fast inhibition in the nervous system is commonly mediated by GABA A receptors comprised of 2␣/2␤/1␥ subunits. In contrast, GABA C receptors containing only subunits (1-3) have been predominantly detected in the retina. However, here using reverse transcription-PCR and in situ hybridization we show that mRNA encoding the 1 subunit is highly expressed in brainstem neurons. Immunohistochemistry localized the 1 subunit to neurons at light and electron microscopic levels, where it was detected at synaptic junctions. Application of the GABA C receptor agonist cis-4-aminocrotonic acid (100 -800 M) requires the 1 subunit to elicit responses, which surprisingly are blocked independently by antagonists to GABA A (bicuculline, 10 M) and GABA C [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA); 40 -160 M] receptors. Responses to GABA C agonists were also enhanced by the GABA A receptor modulator pentobarbitone (300 M). Spontaneous and evoked IPSPs were reduced in amplitude but never abolished by TPMPA, but were completely blocked by bicuculline. We therefore tested the hypothesis that GABA A and GABA C subunits formed a heteromeric receptor. Immunohistochemistry indicated that 1 and ␣1 subunits were colocalized at light and electron microscopic levels. Electrophysiology revealed that responses to GABA C receptor agonists were enhanced by the GABA A receptor modulator zolpidem (500 nM), which acts on the ␣1 subunit when the ␥2 subunit is also present. Finally, coimmunoprecipitation indicated that the 1 subunit formed complexes that also contained ␣1 and ␥2 subunits. Taken together these separate lines of evidence suggest that the effects of GABA in central neurons can be mediated by heteromeric complexes of GABA A and GABA C receptor subunits.

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CIS‐ AND TRANS‐4‐AMINOCROTONIC ACID AS GABA ANALOGUES OF RESTRICTED CONFORMATION

Cited by 175 publications

References 20 publications

γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT

γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT

Transient expression of a novel type of GABA response in rat CA3 hippocampal neurones during development.

Evidence for Inhibition Mediated by Coassembly of GABA_Aand GABA_CReceptor Subunits in Native Central Neurons

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CIS‐ AND TRANS‐4‐AMINOCROTONIC ACID AS GABA ANALOGUES OF RESTRICTED CONFORMATION

Cited by 175 publications

References 20 publications

γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT

γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT

Transient expression of a novel type of GABA response in rat CA3 hippocampal neurones during development.

Evidence for Inhibition Mediated by Coassembly of GABAAand GABACReceptor Subunits in Native Central Neurons

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Evidence for Inhibition Mediated by Coassembly of GABA_Aand GABA_CReceptor Subunits in Native Central Neurons