Search results for "Channel blocker"

18F-fluorodeoxyglucose hypometabolism in cerebellar tonsil and flocculus in downbeat nystagmus.

2006

A patient with downbeat nystagmus was examined by F-fluorodeoxyglucose-positron emission tomography once while off and twice while on successful treatment with 4-aminopyridine. All positron emission tomography scans of the patient showed a reduced cerebral glucose metabolism bilaterally in the region of the cerebellar tonsil and flocculus/paraflocculus when compared with a normal database of the whole brain. An additional region-of-interest analysis revealed that 4-aminopyridine treatment lessened the hypometabolism. This finding supports the hypothesis that the cerebellar tonsil and (para-) flocculus play a crucial role in downbeat nystagmus. The hypometabolism might reflect reduced inhibi…

Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric oxide pathways.

2004

We aimed to investigate the role of K(+) channels and nitric oxide (NO) on the relaxant effects of arachidonic acid in the human intralobar pulmonary arteries. Arachidonic acid produced a concentration-dependent relaxation (E(max)=93+/-3% of maximal relaxation induced by papaverine 0.1 mM;-log EC(30)=7.03+/-0.09) that was antagonized by the cyclooxygenase inhibitor indomethacin (1 microM), by the combination of cyclooxygenase blockade and cytochrome P450 (CYP) blockade with 17-octadecynoic acid (17-ODYA, 10 microM), by the combination of cyclooxygenase inhibition and NO synthase (NOS) inhibition with N(omega)-nitro-l-arginine (l-NOARG, 100 microM), by the simultaneous inhibition of CYP and …

Vasodilator Effects of Liriodenine and Norushinsunine, Two Aporphine Alkaloids Isolated from <i>Annona cherimolia,</i>in Rat Aorta

1995

The effect of two aporphines, liriodenine and norushinsunine, isolated from Annona cherimolia, were studied in the rat aorta in order to examine their mechanism of action. Both alkaloids (10–7–10–4 mol/l) showed relaxant effects on the contractions elicited by 10–6 mol/l noradrenaline (NA) or 80 mmol/l KC1, but, while liriodenine showed a nonspecific relaxant action on both spasmogens, norushinsunine was more potent on KC1-induced contraction. In Ca2+-free medium, both alkaloids (0.1 mmol/l) inhibited the responses elicited by NA, but not those elicited by caffeine. This inhibitory action occurred when the alkaloids were present during the release of the Ca2+ internal stores or during the r…

Cardiovascular effects induced by rolipram, a selective cAMP phosphodiesterase inhibitor: Interaction with adrenergic and calcium affecting drugs

1990

Biochemical Characterization of a Novel Channel-Activating Site on Nicotinic Acetylcholine Receptors

1993

We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine and several structurally related compounds with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membrane vesicles, direct binding studies and photoaffinity labeling. (-)Physostigmine acts as a channel-activating ligand at low concentrations and as a direct channel blocker at elevated concentrations. Channel activation is not inhibited by desensitizing concentrations of ACh or ACh-competitive ligands (including alpha-bungarotoxin and D-tubocurarine) but is inhibited by antibody FK1 and several other compoun…

Kinetics and state-dependent effects of verapamil on cardiac L-type calcium channels.

1996

The voltage dependence and the kinetics of block by verapamil of L-type calcium current (ICa) were investigated in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. ICa was elicited repetitively in response to depolarizing voltage pulses from -80 mV to 0 mV at different pulse intervals and durations. Verapamil reduced the magnitude of ICa in a frequency-dependent manner without tonic component. The time course of ICa remained unchanged suggesting that not open but inactivated channels were affected by the drug. The interaction of verapamil with inactivated channels was investigated by the application of twin pulses. In the presence of verapamil, the duration o…

Inhibition of neuroeffector transmission in human vas deferens by sildenafil

2000

Sildenafil (0.1 - 30 microM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 - 100 microM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 - 100 microM) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 - 30 microM) but it was abolished by the K(+) channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM). Sildenafil, zaprinast and SNP…

TRESK channel contributes to depolarization-induced shunting inhibition and modulates epileptic seizures.

2020

Glutamatergic and GABAergic synaptic transmission controls excitation and inhibition of postsynaptic neurons, whereas activity of ion channels modulates neuronal intrinsic excitability. However, it is unclear how excessive neuronal excitation affects intrinsic inhibition to regain homeostatic stability under physiological or pathophysiological conditions. Here, we report that a seizure-like sustained depolarization can induce short-term inhibition of hippocampal CA3 neurons via a mechanism of membrane shunting. This depolarization-induced shunting inhibition (DShI) mediates a non-synaptic, but neuronal intrinsic, short-term plasticity that is able to suppress action potential generation and…

Three distinct types of voltage-dependent K+ channels are expressed by Müller (glial) cells of the rabbit retina.

1994

There is ample evidence that retinal radial glial (Müller) cells play a crucial role in retinal ion homeostasis. Nevertheless, data on the particular types of ion channels mediating this function are very rare and incomplete; this holds especially for mammalian Müller cells. Thus, the whole-cell variation of the patch-clamp technique was used to study voltage-dependent currents in Müller cells from adult rabbit retinae. The membrane of Müller cells was almost exclusively permeable to K+ ions, as no significant currents could be evoked in K(+)-free internal and external solutions, external Ba2+ (1 mM) reversibly blocked most membrane currents, and external Cs+ ions (5 mM) blocked all inward …

Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures

1993

Rat cortical cells were incubated with the Scrapie prion protein, PrionSc. At concentrations of 3 ng/ml of PrionSc and higher, the viability of the cells decreased significantly after a 12-h incubation period. Simultaneously, the degree of DNA fragmentation increased. In control experiments with antibodies against PrionSc, PrionSc lost its deleterious effect on neurons. PrionSc did not affect the viability of astrocytes. Drugs known to block NMDA receptor channels, such as memantine (1-amino-3,5-dimethyl-adamantane) (Mem), its analogue 1-N-methylamino-3,5-dimethyl-adamantane as well as (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) prevented the effect of …