Search results for "verapamil"
showing 10 items of 68 documents
Multixenobiotic resistance efflux activity in Daphnia magna and Lumbriculus variegatus
2014
Multixenobiotic resistance is a phenomenon in which ATP-binding cassette (ABC) family proteins transfer harmful compounds out of cells. Daphnia magna and Lumbriculus variegatus are model species in aquatic ecotoxicology, but the presence and activity of ABC proteins have not been well described in these species. The aim of this work was to study the presence, activity, and inhibition of ABC transport proteins in D. magna and L. variegatus. The presence of abcb1 and abcc transcripts in 8-9-day-old D. magna was investigated by qRT-PCR. The activity of MXR in D. magna and L. variegatus was explored by influx of the fluorescent ABC protein substrates rhodamine B and calcein-AM, with and without…
Functional evidence of multidrug resistance transporters (MDR) in rodent olfactory epithelium.
2012
WOS: 000305340700029; International audience; BACKGROUND: P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated. PRINCIPAL FINDINGS: Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM) accumulation assay on acute rat and mouse olfactory tissue slices.…
Calcium antagonist properties of cinnarizine, trifluoperazine and verapamil in guinea-pig normal and skinned trachealis muscle.
1990
In guinea-pig trachealis, depolarized by a K(+)-rich medium, Ca2+ (0.01-10 mM) caused concentration-related spasm. Verapamil (0.5-5 microM), cinnarizine (10-100 microM) and trifluoperazine (16-160 microM) each produced concentration-dependent antagonism of Ca2+ characterized by a rightward and downward displacement of the log concentration-effect curve for Ca2+. The rank order of potencies of these antagonists, measured as the IC75 against Ca2+ (10 mM)-induced contraction of depolarized trachea, was verapamil (5.6 microM) greater than cinnarizine (59 microM) greater than trifluoperazine (91 microM). In skinned trachea, verapamil in concentrations up to 100 microM did not modify the concentr…
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.
2001
The expression of P-glycoprotein is induced in cell cultures upon exposure to various inducers. Therefore, the aim of the present study was to evaluate the in-vivo relevance of this observation, i.e. the influence of chronic pretreatments with selected drugs -- all of which are ligands to P-glycoprotein (P-gp) as demonstrated in radioligand binding studies and all of which have some or a considerable effect on P-gp expression in Caco-2 cells -- on the effective intestinal permeabilities of the model compound talinolol in rats employing in-situ single-pass intestinal perfusion of three different gut segments. Talinolol was selected, because it shows high selectivity for one of the exsorptive…
Effects of Calcium Antagonists on Rat Normal and Skinned Fundus
1992
Abstract Calcium chloride (CaCl2) (0·1−25 Mm, in K+-depolarized tissue), KCl (10−112 Mm) and acetylcholine (1 × 10−9 m−1 Mm) produced concentration-dependent contractions of rat isolated fundus. Verapamil (0·01−100 μm), cinnarizine (1−100 μm), trifluoperazine (10−500 μm) and dantrolene (50−250 μm) each produced a concentration-related rightward and downward shift of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (25 Mm)-induced contraction of depolarized fundus, was verapamil (2.5 μm) > cinnarizine (8·7 μm) > trifluoperazine (85·1 μm) > dantrolene (> 250 μm). Cinnarizine (0·5 Mm) a…
EFFECTS OF D-600 AND ITS OPTICAL ISOMERS ON FORCE OF CONTRACTION IN CAT PAPILLARY MUSCLES AND GUINEA-PIG AURICLES
1977
Abstract 1 (--)-D-600 and (+)-D-600 exerted concentration-dependent negative inotropic effects in papillary muscles from cats, the potency of (--)-D-600 being about 100 times greater than that of (+)-D-600. The action was more pronounced at high than at low frequencies of stimulation. Time to peak force, relaxation time and therefore also total duration of contraction were not significantly affected by the drugs. 2 The negative inotropic effects of both drugs were not reversible after washing in drug-free solution for 60 min at all concentrations tested. 3 The same negative inotropic effects were seen in guinea-pig left auricles with the racemic mixture of both isomers. 4 Uptake measurement…
Acceleration of glutathione efflux and inhibition of gamma-glutamyltranspeptidase sensitize metastatic B16 melanoma cells to endothelium-induced cyto…
2005
Highly metastatic B16 melanoma (B16M)-F10 cells, as compared with the low metastatic B16M-F1 line, have higher GSH content and preferentially overexpress BCL-2. In addition to its anti-apoptotic properties, BCL-2 inhibits efflux of GSH from B16M-F10 cells and thereby may facilitate metastatic cell resistance against endothelium-induced oxidative/nitrosative stress. Thus, we investigated in B16M-F10 cells which molecular mechanisms channel GSH release and whether their modulation may influence metastatic activity. GSH efflux was abolished in multidrug resistance protein 1 knock-out (MRP-/-1) B16M-F10 transfected with the Bcl-2 gene or in MRP-/-1 B16M-F10 cells incubated with l-methionine, wh…
Different mechanisms of the inhibition of the transient outward current in rat ventricular myocytes.
1994
The mechanism of drug-induced inhibition of the transient outward current, Ito, has been investigated in rat ventricular myocytes using the whole cell patch clamp technique. Ito was activated by 300 ms depolarizing voltage clamp steps in 10 mV increments from −50 mV up to +40 mV. At +40 mV, Ito peaked after about 3 ms, and the time course of inactivation was appropriately described by two time constants, τfast = 17 ms and τslow = 203 ms. Verapamil, quinidine sulfate and nifedipine preferentially depressed Ito at the end of the 300 ms depolarizing voltage clamp step; the inactivation of Ito was accelerated by all drugs, whereas peak Ito was less affected. The time course of drug action at +4…
Noninvasive blood pressure monitoring evaluation of verapamil slow-release 240-mg antihypertensive effectiveness
1989
The aim of our study was to evaluate the antihypertensive effectiveness of verapamil slow-release (SR), administered once a day. We studied 11 patients, 7 male and 4 female, with an average age of 53.6 +/- 12.86 years, who had essential hypertension. After a drug washout period of at least 15 days, placebo was administered (one tablet per day), and then patients received verapamil SR 240 mg/day at 8:00 a.m. for at least 2 weeks. At the end of the washout, placebo, and active drug treatment periods we performed ambulatory intermittent blood pressure monitoring for 24 h using a Squibb Spacelabs pressurometer. After verapamil treatment, in comparison to placebo, a significant reduction of syst…
Modelling intestinal absorption of salbutamol sulphate in rats
2005
The objective was to develop a semiphysiological population pharmacokinetic model that describes the complex salbutamol sulphate absorption in rat small intestine. In situ techniques were used to characterize the salbutamol sulphate absorption at different concentrations (range: 0.15-18 mM). Salbutamol sulphate at concentration of 0.29 mM was administered in presence of verapamil (10 and 20 mM), grapefruit juice and sodium azide (NaN3) (0.3, 3 and 6 mM). Different pharmacokinetic models were fitted to the dataset using NONMEM. Parametric and non-parametric bootstrap analyses were employed as internal model evaluation techniques. The validated model suggested instantaneous equilibrium betwee…