Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels

Nature ◽  
1989 ◽  
Vol 341 (6239) ◽  
pp. 233-236 ◽  
Author(s):  
Patrik Rorsman ◽  
Per-Olof Berggren ◽  
Krister Bokvist ◽  
Hans Ericson ◽  
Hanns Möhler ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Chloride Channels ◽  
Glucagon Secretion ◽  
Glucose Inhibition

Involvement of GABAA receptor-associated chloride channels in the peripheral antinociceptive effect induced by GABAA receptor agonist muscimol

2007 ◽  
Vol 564 (1-3) ◽  
pp. 112-115 ◽  
Author(s):  
Glaucia Reis ◽  
Daniela Pacheco ◽  
Janetti Francischi ◽  
Maria Castro ◽  
Andréa Perez ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Chloride Channels ◽  
Receptor Agonist ◽  
Antinociceptive Effect

Functional diversity of GABAA receptor ligand-gated chloride channels in rat synaptoneurosomes

Synapse ◽  
1995 ◽  
Vol 19 (3) ◽  
pp. 188-196 ◽  
Author(s):  
Yoshihisa Ito ◽  
Katsuya Segawa ◽  
Hideomi Fukuda
Keyword(s):  
Gabaa Receptor ◽  
Functional Diversity ◽  
Chloride Channels ◽  
Receptor Ligand

Norbornan, a new irreversible ligand of the GABAA-receptor chloride channels

1996 ◽  
Vol 121 (4) ◽  
pp. 404-406 ◽  
Author(s):  
A. I. Golovko ◽  
G. A. Sofronov ◽  
T. V. Klyuntina
Keyword(s):  
Gabaa Receptor ◽  
Chloride Channels ◽  
Irreversible Ligand

scholarly journals Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets

Diabetes ◽  
2017 ◽  
Vol 66 (4) ◽  
pp. 960-969 ◽  
Author(s):  
Christopher A. Reissaus ◽  
David W. Piston
Keyword(s):  
Glucagon Secretion ◽  
Glucose Inhibition

Developmental changes of GABAA receptor-chloride channels in rat Meynert neurons

1998 ◽  
Vol 779 (1-2) ◽  
pp. 9-16 ◽  
Author(s):  
Jeong-Seop Rhee ◽  
Young-Ho Jin ◽  
Norio Akaike
Keyword(s):  
Gabaa Receptor ◽  
Chloride Channels ◽  
Developmental Changes

scholarly journals The role of ligand-gated chloride channels in behavioural alterations at elevated CO2 in a cephalopod

2021 ◽  
Author(s):  
Jodi T Thomas ◽  
Blake L Spady ◽  
Philip L Munday ◽  
Sue-Ann Watson
Keyword(s):  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Elevated Co2 ◽  
Chloride Channels ◽  
Marine Invertebrates ◽  
Activity Levels ◽  
Behavioural Changes ◽  
Gabaa Receptor Antagonist ◽  
Ambient Co2

Projected future carbon dioxide (CO2) levels in the ocean can alter marine animal behaviours. Disrupted functioning of γ-aminobutyric acid type A (GABAA) receptors (ligand-gated chloride channels) is suggested to underlie CO2-induced behavioural changes in fish. However, the mechanisms underlying behavioural changes in marine invertebrates are poorly understood. We pharmacologically tested the role of GABA-, glutamate-, acetylcholine- and dopamine-gated chloride channels in CO2-induced behavioural changes in a cephalopod, the two-toned pygmy squid (Idiosepius pygmaeus). We exposed squid to ambient (∼450 µatm) or elevated (∼1,000 µatm) CO2 for seven days. Squid were treated with sham, the GABAA receptor antagonist gabazine, or the non-specific GABAA receptor antagonist picrotoxin, before measurement of conspecific-directed behaviours and activity levels upon mirror exposure. Elevated CO2 increased conspecific-directed attraction and aggression, as well as activity levels. For some CO2-affected behaviours, both gabazine and picrotoxin had a different effect at elevated compared to ambient CO2, providing robust support for the GABA hypothesis within cephalopods. In another behavioural trait, picrotoxin but not gabazine had a different effect in elevated compared to ambient CO2, providing the first pharmacological evidence, in fish and marine invertebrates, for altered functioning of ligand-gated chloride channels, other than the GABAA R, underlying CO2-induced behavioural changes. For some other behaviours, both gabazine and picrotoxin had a similar effect in elevated and ambient CO2, suggesting altered function of ligand-gated chloride channels was not responsible for these CO2-induced changes. Multiple mechanisms may be involved, which could explain the variability in the CO2 and drug treatment effects across behaviours.

scholarly journals Neurosteroids Alter γ-Aminobutyric Acid Postsynaptic Currents in Gonadotropin-Releasing Hormone Neurons: A Possible Mechanism for Direct Steroidal Control

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4366-4375 ◽  
Author(s):  
Shannon D. Sullivan ◽  
Suzanne M. Moenter
Keyword(s):  
Gabaa Receptor ◽  
Decay Time ◽  
Chloride Channels ◽  
Fluorescent Protein ◽  
Brain Slices ◽  
Cell Voltage ◽  
Dehydroepiandrosterone Sulfate ◽  
Postsynaptic Currents ◽  
Gnrh Neurons ◽  
Green Fluorescent

Pulsatile GnRH release is required for fertility and is regulated by steroid feedback. Whether or not steroids or their metabolites act directly on GnRH neurons is not well established. In some neurons, steroid metabolites known as neurosteroids modulate the function of the GABAA receptor. Specifically, the progesterone derivative allopregnanolone is an allosteric agonist at this receptor, whereas the androgen dehydroepiandrosterone sulfate (DHEAS) is an allosteric antagonist. We hypothesized these metabolites act similarly on GnRH neurons to modify the response to GABA. Whole-cell voltage-clamp recordings of GABAergic miniature postsynaptic currents (mPSCs) were made from green fluorescent protein-identified GnRH neurons in brain slices from diestrous mice. Glutamatergic currents were blocked with antagonists and action potentials blocked with tetrodotoxin, minimizing presynaptic effects of treatments. Allopregnanolone (5 μm) increased mPSC rate of rise, amplitude and decay time by 15.9 ± 6.1%, 16.5 ± 6.3%, and 58.3 ± 18.6%, respectively (n = 7 cells). DHEAS (5 μm) reduced mPSC rate of rise (32.1 ± 5.7%) and amplitude (27.6 ± 4.3%) but did not alter decay time (n = 8). Effects of both neurosteroids were dose dependent between 0.1 and 10 μm. In addition to independent actions, DHEAS also reversed effects of allopregnanolone on rate of rise and amplitude so that these parameters were returned to pretreatment baseline values (n = 6). These data indicate allopregnanolone increases and DHEAS decreases responsiveness of GnRH neurons to activation of GABAA receptors by differentially modulating current flow through GABAA receptor chloride channels. This provides one mechanism for direct steroid feedback to GnRH neurons.

scholarly journals γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion

2020 ◽  
Vol 295 (16) ◽  
pp. 5419-5426
Author(s):  
Qian Yu ◽  
Bao Khanh Lai ◽  
Parvin Ahooghalandari ◽  
Anders Helander ◽  
Erik Gylfe ◽  
...  
Keyword(s):  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Human Islets ◽  
Glucagon Release ◽  
Paracrine Factors ◽  
Glucose Inhibition ◽  
Mouse Islets ◽  
Blood Glucose Concentrations ◽  
Effect Of Glucose

Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion.

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