NiCl2 and Amiloride Induce Spreading Depression in Guinea Pig Hippocampal Slices

Spreading depressions (SD) occur in association with ischaemia, epilepsy and migraine. Intracellular calcium oscillations have been suggested to be involved in the generation and propagation of SD. The present study was performed to study the mechanism of conditioning guinea pig hippocampal slices by the T-type calcium channel blockers NiCl2 and amiloride. SD-like fluctuations of DC potential were recorded by inserting microelectrodes into the CA1 and CA3 regions. The SD occurrence was significantly greater with 10 µmol/ l NiCl2 as well as with 25 and 50 µmol/ l amiloride than with other concentrations of these substances. The concentration response curve was inversely U-shaped with the maximum repetition rates of SDs being achieved at 10 µmol/ l NiCl2 as well as at 25 and 50 µmol/ l amiloride. SD occurrence could be completely blocked by the NMDA antagonist APV (10 µmol/ l) in all cases. These data demonstrate that modulation of the Ca2+ dynamics conditioned guinea pig hippocampal slices and increased their susceptibility to generate SD.

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Neutral/negative α1-AR antagonists and calcium channel blockers at comparison in functional tests on guinea-pig smooth muscle and myocardium

Pharmacological Reports ◽

10.1016/j.pharep.2018.10.007 ◽

2019 ◽

Vol 71 (1) ◽

pp. 128-132 ◽

Cited By ~ 2

Author(s):

Matteo Micucci ◽

Alberto Chiarini ◽

Roberta Budriesi

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Channel Blockers ◽

Functional Tests

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Evidence for a Direct Effect on Vascular Permeability of Platelet-Activating Factor Induced Hemoconcentration in the Guinea Pig

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660126 ◽

1985 ◽

Vol 54 (04) ◽

pp. 756-759 ◽

Cited By ~ 24

Author(s):

Dean A Handley ◽

Mark L Lee ◽

Robert N Saunders

Keyword(s):

Guinea Pig ◽

Vascular Permeability ◽

Calcium Channel Blockers ◽

Platelet Activating Factor ◽

Channel Blockers ◽

Heptanoic Acid ◽

Thromboxane Synthetase ◽

Specific Antagonist ◽

Protein Rich ◽

Prior Administration

SummaryThe ability of synthetic platelet-activating factor (PAF) given intravenously to produce loss (extravasation) of protein rich plasma (resulting in hemoconcentration) has been examined using guinea pigs. Hemoconcentration induced by PAF was not prevented by prior administration of inhibitors of thromboxane synthetase (7-(3-pyridyl)heptanoic acid, UK-37,248-01), PGI2, aspirin, indomethacin or antiserum induced thrombocytopenia. Calcium channel blockers (nifedipine, verapamil, diethyl-amino octyltrimethoxybenzoate, diltiazem), antihistamines (pyrilamine, cimetidine, diphenhydramine), or the elevator of cAMP IBMX were ineffective in blocking PAF-induced hemoconcentration. In contrast, CV-3988, reported to be a specific antagonist to PAF, was 98% inhibitory of PAF extravasation when given i. a. at 3.5 mg/kg. The ED50 was 0.14 mg/kg I. A. and 15 mg/kg p.o. against 75 ng/kg PAF. These data suggest that PAF-induced hemoconcentration involves receptor mediated alterations of vascular permeability that are inhibited by a specific PAF antagonist.

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Picrotoxin-induced epileptic activity in hippocampal and neocortical slices (guinea pig): suppression by organic calcium channel blockers

Brain Research ◽

10.1016/s0006-8993(09)90017-8 ◽

1994 ◽

Vol 658 (1-2) ◽

pp. 119-126 ◽

Cited By ~ 19

Author(s):

H. Straub ◽

R. Köhling ◽

E.-J. Speckmann

Keyword(s):

Guinea Pig ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Epileptic Activity ◽

Channel Blockers

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Butylidenephthalide Blocks Potassium Channels and Enhances Basal Tension in Isolated Guinea-Pig Trachea

BioMed Research International ◽

10.1155/2014/875230 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Hsin-Te Hsu ◽

You-Lan Yang ◽

Wan-Chen Chen ◽

Chi-Ming Chen ◽

Wun-Chang Ko

Keyword(s):

Guinea Pig ◽

Calcium Channel Blockers ◽

Relaxation Curve ◽

Antagonistic Effect ◽

Channel Blockers ◽

Krebs Solution ◽

Antagonistic Effects ◽

Individual Effects ◽

Isolated Trachea ◽

The Individual

Butylidenephthalide (Bdph, 30~300 μM), a constituent ofLigusticum chuanxiongHort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 μM), and its tension changes were isometrically recorded. Cromakalim (3 μM), an ATP-dependent K+channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 μM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 μM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 μM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 μM) and 4-aminopiridine (4-AP, 5 mM), a blocker of Kv1 family of K+channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of Kv1 family of K+channels, to enhance the baseline tension of guinea-pig trachea.

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GABAB receptor antagonism by 7-MBFG, a benzo[b]furan analogue of baclofen, in central and peripheral tissues

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y98-096 ◽

1998 ◽

Vol 76 (7-8) ◽

pp. 798-801

Author(s):

Jennifer Ong ◽

David I Kerr ◽

M'Hammed Ansar ◽

Claude Vaccher ◽

Pascal Berthelot

Keyword(s):

Guinea Pig ◽

Response Curve ◽

Gabab Receptor ◽

Guinea Pig Ileum ◽

Butanoic Acid ◽

Peripheral Tissues ◽

Aromatic Character ◽

Rat Neocortex ◽

The Right ◽

Concentration Response Curve

(R,S)-4-Amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid (7-MBFG), a new benzofuran analogue of the GABAB receptor agonist baclofen, has been evaluated for pharmacological activity on GABAB receptors in the guinea-pig isolated ileum and rat neocortical slices. 7-MBFG (300 and 500 µM) reversibly antagonized the (R,S)-baclofen induced depression of cholinergic twitch contractions in the guinea-pig ileum and shifted the concentration-response curve for baclofen to the right, in a parallel manner, giving an apparent pA2 value of 3.7 ± 0.3. Likewise, 7-MBFG (300 and 500 µM) reversibly blocked the baclofen-induced suppression of spontaneous discharges, in rat neocortical slices maintained in Mg2+-free Krebs medium, and caused a rightward, parallel shift of the baclofen concentration-response curve, giving an apparent pA2 value of 4.1 ± 0.1. The compound 7-MBFG belongs to a novel, new class of antagonist at central and peripheral GABAB receptors, in which the antagonist properties reside in the pseudo-aromatic character of their 3-benzo[b]furan-2-yl substituents, and might provide useful leads for further development of GABAB receptor ligands.Key words: (R,S)-baclofen, 4-amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid, GABAB receptor antagonist, rat neocortex, guinea-pig ileum.

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