Antagonist actions of bicuculline methiodide and picrotoxin on extrasynaptic γ-aminobutyric acid receptors

1985 ◽  
Vol 63 (11) ◽  
pp. 1465-1470 ◽  
Author(s):  
A. W. Barolet ◽  
A. Li ◽  
S. Liske ◽  
M. E. Morris
Keyword(s):  
Membrane Conductance ◽  
Aminobutyric Acid ◽  
Maximal Response ◽  
Bicuculline Methiodide ◽  
Low Concentrations ◽  
Agonist And Antagonist ◽  
High Concentrations ◽  
The Right ◽  
Transmitter Uptake ◽  
Concentration Response Curve

The effects of picrotoxin and bicuculline methiodide to block depolarizing responses of extrasynaptic receptors for γ-aminobutyric acid (GABA) are compared using excitability testing of myelinated axons in amphibian peripheral nerve. The actions of the antagonists appear both complex and dissimilar. Picrotoxin (10–1000 μM) produces large reversible depressions of the maximal response to GABA (0.01–10 mM) and increases the EC50 from 0.33 to 12.6 mM. With high concentrations of agonist and antagonist an insensitive component is apparent. The action of picrotoxin is not classically noncompetitive: it may represent a mixed antagonism (competitive and noncompetitive) or a noncompetitive one, masked by the presence of receptor reserve and (or) secondary depolarizing influences (e.g., GABA-evoked [K+]o accumulation). Bicuculline methiodide (10–200 μM) shifts the GABA concentration–response curve to the right; maximal responses persist and are even enhanced. The impression that bicuculline methiodide has a competitive action is supported by analysis of its inhibition of responses to low concentrations of the agonist. It is suggested that the enhancement of GABA responses by bicuculline methiodide and their apparent resistance to block by picrotoxin may be due to a common secondary effect of the antagonists such as a decrease in membrane conductance to K+ and (or) block of transmitter uptake.

Existence of two types of postjunctional α-adrenoceptors in the isolated canine internal carotid artery

1988 ◽  
Vol 66 (5) ◽  
pp. 655-659 ◽  
Author(s):  
Yasuaki Kawai ◽  
Shigeaki Kobayashi ◽  
Toshio Ohhashi
Keyword(s):  
Response Curve ◽  
Carotid Arteries ◽  
Internal Carotid ◽  
The Other ◽  
Low Concentrations ◽  
Selective Agonists ◽  
High Concentrations ◽  
The Right ◽  
Internal Carotid Arteries ◽  
Concentration Response Curve

The pharmacological characteristics of postjunctional α-adrenoceptors in isolated canine internal carotid arteries were investigated by the use of selective agonists and antagonists for α1 and α2-adrenoceptors. Norepinephrine, phenylephrine, and xylazine caused concentration-dependent contractions in the helical strips. The contraction induced by 10−4 M xylazine was significantly smaller than that produced by 10−4 M norepinephrine or 10−4 M phenylephrine. The contraction induced by 10−4 M phenylephrine was almost the same value as that induced by 10−4 M norepinephrine. Phentolamine (10−8 and 10−7 M) caused a parallel shift to the right of the concentration–response curve to norepinephrine. The contractile responses to low concentrations of norepinephrine were significantly suppressed by pretreatment with an α2-antagonist such as yohimbine (10−9 and 10−8 M) or DG 5128(10−7 and 10−6 M). On the other hand, the responses to higher concentrations of norepinephrine were mainly reduced by low concentrations of an α1-antagonist, prazosin (3 × 10−10 and 3 × 10−9 M). These results suggest that both α1- and α2-adrenoceptors are located on the plasma membrane of smooth muscle cells in canine internal carotid arteries and that the norepinephrine-induced contractions at low and high concentrations are mainly mediated by activation of α2- and α1-adrenoceptors, respectively.

scholarly journals Large enhancement of canine taste responses to sugars by salts.

1990 ◽  
Vol 95 (5) ◽  
pp. 1007-1018 ◽  
Author(s):  
T Kumazawa ◽  
K Kurihara
Keyword(s):  
Maximal Response ◽  
Chorda Tympani ◽  
Chorda Tympani Nerve ◽  
Glucose Response ◽  
Low Concentrations ◽  
Large Enhancement ◽  
High Concentrations ◽  
Apical Membranes ◽  
The Hill ◽  
Concentration Response Curve

The effects of changed ionic environments on the canine taste responses to sugars were examined by recording the activity of the chorda tympani nerve. a) The responses to various sugars were greatly enhanced by the presence of salts having monovalent cations such as Na+, K+, choline+, or Tris+. The responses to sugars were suppressed by high concentrations of salts. (b) The presence of 100 mM NaCl in fructose solution did not affect the maximal response and changed the Hill constant for the concentration-response relationship from 1.3 to 2.4. (c) CaCl2 greatly enhanced the response to fructose, while MgCl2 exhibited practically no effect. The presence of 20 mM CaCl2 in fructose solution changed the Hill constant from 1.2 to 2.4. (d) CaCl2 suppressed the responses to 0.5 M sugars except for fructose and sucrose and enhanced the responses to all sugars examined at 1 M. In the glucose response, the slope of the concentration-response curve was increased by the presence of CaCl2. Here the curve in the absence of CaCl2 intersected with that in the presence of CaCl2, indicating that CaCl2 suppressed the response to glucose of low concentrations and enhanced that of high concentrations. (e) The enhancement of the sugar responses by salts was not simply explained in terms of ionic permeability at the apical membranes of taste cells. The enhanced and suppressed effects of salts on the sugar responses were interpreted in terms of the cooperativity between receptor molecules for sugars.

scholarly journals Endothelin-Induced Contraction and Relaxation of Rat Isolated Basilar Artery: Effect of BQ-123

1994 ◽  
Vol 14 (5) ◽  
pp. 845-852 ◽  
Author(s):  
G. I. Feger ◽  
L. Schilling ◽  
H. Ehrenreich ◽  
M. Wahl
Keyword(s):  
Nitric Oxide ◽  
Basilar Artery ◽  
Competitive Inhibition ◽  
Regression Curve ◽  
Low Concentrations ◽  
Small Contraction ◽  
The Right ◽  
Contraction And Relaxation ◽  
Oxide Synthase ◽  
Concentration Response Curve

In ring segments from rat basilar artery (BA) the endothelin (ET) peptides ET-1, ET-2, and ET-3 induced concentration-related contractions. The order of potency was ET-1 = ET-2 > ET-3, while no differences occurred in the maximum contraction. The selective ETA receptor antagonist, BQ-123 (10−10-10−4 M) alone elicited a small contraction only at 10−4 M. In the presence of BQ-123 (10−7-10−5 M), the concentration-response curve for ET-1 was shifted to the right without any decrease in maximum contraction, indicating competitive inhibition of ET-1 binding to the ETA receptor by BQ-123. The pA2 value calculated for BQ-123 was 6.935; the slope of the regression curve was 0.734. In contrast to ET-1, the contractile action of ET-3 was abolished by 10−5 M BQ-123. In segments precontracted with 10−6 M serotonin, ET-3, but not ET-1, induced relaxation at low concentrations (10−11-10−8 M), with maximum relaxation amounting to 17.8 ± 14.7% of precontraction (mean ± SD; n = 16). The relaxant action of ET-3 was abolished in vessels incubated with NG-nitro-l-arginine (10−5 M), an inhibitor of nitric oxide synthase. These results indicate that the ET-induced contraction of the isolated rat BA involves activation of the ETA receptor. The ET-3-induced relaxation of precontracted rat BA is apparently mediated by release of nitric oxide from the endothelium.

scholarly journals The interaction of atoms and molecules with solid surfaces XII—Critical phenomena in a two-dimensional gas

1937 ◽  
Vol 163 (912) ◽  
pp. 132-138 ◽  
Keyword(s):  
Critical Temperature ◽  
Equation Of State ◽  
Critical Phenomena ◽  
Three Dimensional ◽  
Inert Gases ◽  
Two Dimensional ◽  
Lennard Jones ◽  
Low Concentrations ◽  
High Concentrations ◽  
The Right

In a paper recently published by Professor Lennard-Jones and the author (Lennard-Jones and Devonshire 1937) the equation of state of a gas at high concentrations has been calculated in terms of the interatomic fields. The equation found had the right kind of properties and, in particular, using the interatomic fields previously determined from the observed equation of state at low concentrations (Lennard-Jones 1931), the critical temperature was given correctly to within a few degrees for the inert gases. In this paper we shall apply the same method to determine the equation of state of a two-dimensional gas. Although such a gas cannot strictly be obtained in practice, an inert gas adsorbed on a surface (or in fact any gas held by van der Waals’ forces only) would probably behave very much like one, the fluctuations of the potential field over the surface not being of much importance. In confirmation of this it may be noted that the specific heat of argon adsorbed on charcoal was found by Simon (Simon 1935) to be equal to that of a perfect two-dimensional gas down to 60° K. A gas adsorbed on a liquid would be an even better representation of a two-dimensional one. Some measurements on the adsorption of krypton and xenon on liquid mercury have been made by Cassel and Neugebauer (Cassel and Neugebauer 1936), and they found no trace of any critical phenomena though they worked at temperatures considerably below the critical temperature of xenon. Our results are in agreement with this, for they show that the critical temperature of a two-dimensional gas should be about half that of the corresponding three-dimensional one.

Modulation of Chelidonii herba on GABA Activated Choride Current in Rat PAG Neurons

2001 ◽  
Vol 29 (02) ◽  
pp. 265-279 ◽  
Author(s):  
Yonjung Kim ◽  
Minchul Shin ◽  
Jooho Chung ◽  
Eehwa Kim ◽  
Gyosung Koo ◽  
...  
Keyword(s):  
G Proteins ◽  
Inhibitory Action ◽  
Ion Current ◽  
Aminobutyric Acid ◽  
Patch Clamp Technique ◽  
Gtp Binding ◽  
Inhibitory Modulation ◽  
Low Concentrations ◽  
High Concentrations ◽  
Perforated Patch Clamp

Modulation of Chelidonii herba on γ-aminobutyric acid (GABA) activated chloride current in the acutely dissociated periaqueductal gray (PAG) neuron was studied by nystatin-perforated patch-clamp technique. High concentrations of Chelidonii herba elicited ion current, that was blocked by bicuculline. Low concentrations reduced the GABA activated current in PAG. Two types of inhibitory action of Chelidonii herba on GABA activated current have been implicated in PAG. One is the inhibitory action of Chelidonii herbe on GABA was abolished by naltrexone and the other is that of Chelidonii herba was potentiated by naltrexone. In addition, all of two types of action of Chelidonii herba are linked to pertussis toxin-sensitive GTP-binding proteins. These results suggest that the inhibitory modulation of Chelidonii herba on GABA activated current via G-proteins in PAG neuron is an important analgesic mechanism.

d-Serine inhibits AMPA receptor-mediated current in rat hippocampal neurons

2007 ◽  
Vol 85 (5) ◽  
pp. 546-555 ◽  
Author(s):  
Xiang-Qun Gong ◽  
Rebecca L. Zabek ◽  
Donglin Bai
Keyword(s):  
Amino Acids ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Binding Pocket ◽  
Maximal Response ◽  
Competitive Antagonist ◽  
The Right ◽  
Concentration Response Curve ◽  
Native Ligand

d-Serine, a recently identified gliotransmitter, serves as an endogenous coagonist binding to the glycine site of N-methyl-d-aspartate (NMDA) receptors. However, it is not clear whether this native ligand is able to bind to and modulate α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptors. In the present study, we showed that d-serine was able to concentration-dependently inhibit kainate-induced AMPA receptor-mediated current in acutely isolated hippocampal neurons. The blocking action of d-serine on AMPA receptors was characterized by a shift in concentration–response curve of kainate-induced current to the right with no change in the maximal response and independent of holding potential in the range of –80 to +60 mV. This is consistent with a model that d-serine is a competitive antagonist on AMPA receptors. In contrast, l-serine did not exert such an inhibitory action. Consistent with this observation, we found that several d-isoforms, but not l-isoforms, of endogenous and exogenous amino acids were able to block AMPA receptors. These results indicate that there is a low affinity and stereo-selective site at the agonist binding pocket of AMPA receptors for these d-amino acids. More importantly, vesicular-released endogenous d-serine from astrocytes could potentially modulate AMPA receptors in synaptic transmission in hippocampus.

scholarly journals Comparative effect of Nickel and beta-aminobutiric Acid on some Secondary Metabolits of Echium amoenum

2015 ◽  
Vol 9 (5) ◽  
pp. 25-30 ◽  
Author(s):  
Peyman Rajaei ◽  
Neda Mohamadi
Keyword(s):  
Secondary Metabolites ◽  
Dry Weight ◽  
Aminobutyric Acid ◽  
Stress Effects ◽  
Low Concentrations ◽  
Iranian Traditional Medicine ◽  
Wonderful Variety ◽  
Research Findings ◽  
Echium Amoenum ◽  
High Concentrations

Plants have a wonderful variety of secondary metabolites which may be change due to environmental factors and stress conditions. Considering the importance of Echium amoenum in Iranian traditional medicine, this study aimed to investigate the effect of abiotic stresses on the possibility of further production of secondary metabolites in the plant. In general, according our research findings, beta-aminobutyric acid increased growth indexes. Effect of BABA on secondary metabolites was different. BABA increased plant flavonoids but reduced the tannins. Numerous studies have pointed to the stress effects of this material at high concentrations but the concentrations used in this study increased the plant growth. Nickel in applied concentrations had no significant reduction in plant dry weight but increased the photosynthetic pigments. Ni increased plant flavonoids but reduced the tannins. Nickel and beta-aminobutyric acid at low concentrations, is recommended to use for greater production of secondary metabolites in Echium cultivation.DOI: http://dx.doi.org/10.3126/ijls.v9i5.12687

scholarly journals Evidence that acetylcholine is an inhibitory transmitter of heart interneurons in the leech

1992 ◽  
Vol 171 (1) ◽  
pp. 329-347
Author(s):  
J. Schmidt ◽  
R. L. Calabrese
Keyword(s):  
Membrane Potential ◽  
Motor Neurons ◽  
Membrane Conductance ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Bicuculline Methiodide ◽  
Postsynaptic Receptors ◽  
Postsynaptic Potential ◽  
Inhibitory Transmitter ◽  
Cl Conductance

1. In the leech, synaptic transmission between heart interneurons (HN cells) and between HN cells and heart motor neurons (HE cells) is blocked by bicuculline methiodide. 2. Gamma-aminobutyric acid, when applied focally onto the somata of HN cells or when added to the superfusate, has no effect on the membrane potential of HN cells. 3. Both acetylcholine (ACh) and the ACh agonist carbachol hyperpolarize HN cells and HE cells when applied focally onto their somata or into the neuropil or when added to the superfusate. 4. Inhibitory postsynaptic-potential-like responses elicited by focal application of carbachol onto the somata of HN cells and HE cells are blocked by bicuculline methiodide and are reversed when Cl- is injected into the cells. 5. Focal application of carbachol onto the somata of HN cells and HE cells increases membrane conductance. 6. The results indicate that HN cells use ACh as an inhibitory transmitter, that the postsynaptic receptors for ACh are blocked by bicuculline methiodide and that inhibition of HN cells and HE cells is mediated by an increased Cl- conductance.

scholarly journals Immunoglobulin E decapeptide-induced 5-hydroxytryptamine release from rat peritoneal mast cells. Comparison with corticotropin-(1–24)-peptide, polyarginine, polylysine and antigen

1981 ◽  
Vol 198 (3) ◽  
pp. 615-619 ◽  
Author(s):  
J W Coleman ◽  
S T Holgate ◽  
M K Church ◽  
R C Godfrey
Keyword(s):  
Mast Cells ◽  
Benzalkonium Chloride ◽  
Immunoglobulin E ◽  
Response Curves ◽  
Low Concentrations ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells ◽  
High Concentrations ◽  
Concentration Response Curve ◽  
Net Release

A synthetic basic decapeptide from the C4 domain of human immunoglobulin E, corticotropin-(1-24)-peptide, polyarginine and polylysine stimulated up to 90% net release of 5-hydroxytryptamine from mast cells in rat peritoneal-cell suspensions. Concentration-response curves to all four polypeptides were parallel. Polyarginine and polylysine (EC50 congruent to 0.05 microM) were approximately 100-fold more potent than immunoglobulin E decapeptide and corticotropin-(1-24)-peptide (EC50 congruent to 5 microM). Polypeptide-induced release was complete within 5-10s. Immunoglobulin-E-decapeptide-induced 5-hydroxytryptamine release was additive to that induced by low concentrations of polyarginine, but non-additive to that induced by high concentrations of polyarginine. In contrast, release induced by antigen was additive along the whole length of the concentration-response curve to polyarginine. Benzalkonium chloride inhibited immunoglobulin-E-decapeptide- and polyarginine-induced 5-hydroxytryptamine release but enhanced release induced by immunological stimulation.

Effect of pretreatment of long-term ovariectomized rats with an LRH antagonist on LH release in vitro by LRH, elevated K+ or N6-monobutyryl adenosine 3',5'-monophosphate (mbcAMP) plus theophylline

1985 ◽  
Vol 108 (3) ◽  
pp. 331-337 ◽  
Author(s):  
G. P. van Rees ◽  
J. A. M.J. van Dieten
Keyword(s):  
Ovariectomized Rats ◽  
Serum Lh ◽  
Low Concentrations ◽  
Pituitary Glands ◽  
Lh Release ◽  
Release In Vitro ◽  
High Concentrations ◽  
Response Line ◽  
The Right

Abstract. The effect of the LRH antagonist (Ac-D-p--Cl-Phe1,2,D-Trp3,D-Phe6-D-Ala10)-LRH (Org 30093) on pituitary LH release was studied, using pituitary glands of ovariectomized rats. In vitro, the antagonist had no detectable agonist activity in the concentration used, had no effect on the maximal LH release which can be induced by LRH and shifted the dose-response line of LRH to the right, without changing its slope. By this the antagonist fulfilled the conditions of purely competitive antagonist. Also, when present in vitro, the antagonist had no effect on LH release induced by raised K+, whether alone or in combination with mbcAMP plus theophylline. A single injection of Org 30093 decreased serum LH without inducing a change of pituitary LH content measured 24 h later. Twenty-four h after the sc injection of the agonist, LH release in vitro induced by LRH was affected differently, depending on the concentration of LRH used: the effect of low concentrations of LRH was inhibited, whereas the effect of high concentrations of LRH was augmented. Pretreatment with the agonist had no effect on LH release by raised K+ combined with mbcAMP plus theophylline, but slightly increased LH release by raised K+.

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