cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.

Heuschneider, G; Schwartz, Rochelle D.

doi:10.1073/pnas.86.8.2938

Cited by 85 publications

(35 citation statements)

References 39 publications

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“…Phorbol esters decrease the ACB response of chick sympathetic neurons in a similar manner (Downing and Role, 1987). Phorbol esters also reversibly decrease the ACh response of chick myotubes (Eusebi et al, 1985), and CAMP analogs decrease the function of GABA receptors in rat brain synaptosomes (Heuschneider and Schwartz, 1989).…”

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confidence: 98%

Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit

et al. 1990

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Chick ciliary ganglion neurons have nicotinic acetylcholine receptors (AChRs) that mediate synaptic transmission through the ganglion. A cAMP- dependent process has previously been shown to enhance the ACh response of the neurons 2- to 3-fold without requiring the synthesis of new receptors. We show here that the receptors can be phosphorylated in situ by a cAMP-dependent process. The phosphorylation occurs predominantly on components of 50 and 58 kDa. Both derive from putative ligand-binding alpha 3 subunits, with the smaller phosphorylated species probably representing a degradation product of the larger. The increase in receptor phosphorylation caused by incubating the neurons with a cAMP analog parallels the increase observed in the ACh response, with respect to both time course and relative extent. The phosphorylation of ciliary ganglion AChRs differs from that reported for electric organ AChRs, which occurs primarily on the non-ligand- binding gamma and delta subunits and increases the rate of agonist- induced receptor desensitization.

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confidence: 98%

Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit

et al. 1990

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“…Stimulation of second messenger systems may have resulted in a reduction of GABAR currents probably by phosphorylation of GABAR protein. Cyclic AMP and the adenylate cyclase activator forskolin decreased GABA-gated Cl − flux in rat cortical synaptoneurosomes [21]. The catalytic subunit cyclic AMP-dependent protein kinase (cPKA) when injected into cultured mouse spinal cord neurons reduced GABAR currents [22].…”

Section: Reduction In Gabar Sensitivity For Gabamentioning

confidence: 99%

Experimental status epilepticus alters γ‐aminobutyric acid type A receptor function in CA1 pyramidal neurons

Kapur

Coulter

1995

Annals of Neurology

113

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There is a reduction of γ-aminobutyric acid (GABA)-mediated inhibition in the CA1 pyramidal region of the hippocampus during status epilepticus (SE). The cellular basis of this loss of GABAmediated inhibition is not known. This study tested the possibility that GABA type A (GABA A ) receptor function in CA1 pyramidal neurons was reduced or blocked during SE, at least in part by postsynaptic cellular mechanisms. GABA A , receptor currents (I GABA ) were studied by whole-cell patch-clamp techniques in CA1 pyramidal neurons acutely dissociated from rats undergoing lithium/pilocarpine-induced limbic status epilepticus (SE neurons) and from naive rats (naive neurons). SE neurons had more depolarized resting membrane potential (−17.3 mV) compared with naive neurons (−56 mV). I GABA was absent in 47% of SE neurons and reduced in 55% of the remainder, compared with naive neurons. The reduction in I GABA in SE neurons resulted from a combination of factors, including reduced potency and reduced efficacy of GABA in activating chloride channels, and diminished driving force for the GABA-induced chloride currents once activated. These postsynaptic cellular mechanisms resulted in a net reduction or loss in GABAmediated inhibition and may explain previous in vivo findings reporting a loss of inhibition in hippocampus during limbic SE.Convulsive status epilepticus (SE) is a medical emergency that can result in brain damage or even death. While death following treated SE is usually a consequence of the underlying cause of SE, mortality is also related to seizure duration [1]. Neurologic morbidity including neuropsychological dysfunction [2], increased risk for subsequent seizures, and a low incidence of spontaneous remission of underlying epilepsy is associated with SE [2]. Improvement in prognosis of patients with SE will result from a better understanding of the pathophysiology of SE. A key to understanding the pathophysiology of SE was the development and validation of various animal models of this disorder. One such model initially described by Honchar and colleagues [3] was based on cholinergic stimulation of the brain by sequential administration of lithium and pilocarpine. Treiman and associates [4] found that a predictable sequence of electroencephalographic (EEG) changes that occurred during the course of human convulsive SE was replicated in lithium/pilocarpine-induced SE in rats [5]. In addition, the profile of efficacy of anticonvulsants in an animal model of SE was similar to that in human convulsive SE [6].There is a critical role for loss of γ-aminobutyric acid type A (GABA A )-mediated inhibition in the CA1 region of the hippocampus in partial onset SE in experimental animals [7]. SE induced by lithium and pilocarpine resulted in reduction of the number of GABA A receptors (GABARs) in the rat forebrain; and injection of a combination of lithium and pilocarpine resulted in reduction of GABA A -mediated inhibition in the CA1 region of the hippocampus

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“…In synaptosomes, cAMP analogs and the adenylate cyclase activator forskolin decrease GABA-gated Cl-flux (14,15). These compounds also reduce the peak current evoked by GABA in mouse spinal neurons (16) and increase the rate of decay of the current in cultured cortical (15) and hippocampal neurons (17).…”

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confidence: 99%

Facilitation of GABAergic signaling in the retina by receptors stimulating adenylate cyclase.

Feigenspan

Bormann²

1994

Proc. Natl. Acad. Sci. U.S.A.

101

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The y-/aminobutyric acid type A (GABAA) receptor is the predominant Cl--channel protein mediating inhibition in the retina and elsewhere in the mammalian brain. We have observed a time-dependent increase ofGABA-induced whole-cell currents when dopamine was applied externally to rat retinal amacrine cells. After 20 min, the peak current was increased to 208% ± 10% of its initial value. A comparable effect was observed with the dopamine Di receptor agonist (+)-l-phenyl-2,3,4,5-tetrahydro(lH)-3-benzazepine-7, (21).In the present study we investigated the role of peptides and other transmitter substances such as dopamine, which are colocalized with GABA in the rat retina (22), as possible modulators of GABAA receptor function. Using patch-clamp techniques, we have identified a convergent pathway in amacrine cells that could facilitate GABA-mediated inhibition in the retina. This pathway involved stimulation of adenylate cyclase and phosphorylation of GABAA receptors by PKA. MATERIALS AND METHODSCel Culture. Organotypic retinal slices were prepared from 6-day-old Wistar rats as described (23). Briefly, vertical sections of 125-jum thickness were cut and embedded into a plasma clot made from chicken plasma (Sigma) and thrombin (Sigma). The coverslips were placed in culture tubes (Nunclon, Roskilde, Denmark) and 750 ,4 of culture medium was added. The medium contained 50%o basal medium Eagle (GIBCO), 25% Hanks' balanced salt solution (GIBCO), 25% horse serum (GIBCO), 6.5 mg of glucose per ml (Merck), 1 mM glutamine (Biochrom, Berlin), 3 mM taurine (Sigma), 1 ,.g of vitamin B12 per ml (Sigma), and 10 mM Hepes (Biochrom). After 2 and 3 weeks in culture, amacrine cells were visually identified in the inner nuclear layer of the retina (7,23).Electrophysiology. The preparation was viewed with Nomarski optics at 640x magnification using an inverted Zeiss microscope and continuously perfused (0.5 ml/min) at room temperature (21-250C). The extracellular bath solution contained (in mM) 137 NaCl, 5.4 KCl, 1.8 CaCl2, 1 MgCl2, and 5 Hepes (pH 7.4). Membrane currents were recorded with whole-cell and cell-attached patch-clamp methods (24), using an EPC-9 amplifier (HEKA Electronik, Lambrecht/ Pfalz, Germany). Pipettes were coated with silicone elastomer and then filled with a solution containing (in mM) 120 I-V, current-voltage.

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cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.

Cited by 85 publications

References 39 publications

Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit

Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit

Experimental status epilepticus alters γ‐aminobutyric acid type A receptor function in CA1 pyramidal neurons

Facilitation of GABAergic signaling in the retina by receptors stimulating adenylate cyclase.

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