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Biomedical subjects

G Suarez-Kurtz

Publications and source records attributed to G Suarez-Kurtz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of bovine serum albumin on the calcium release channel of sarcoplasmic reticulum from rabbit skeletal muscle.

The effect of bovine serum albumin (BSA) on the activity of the calcium release channel of the sarcoplasmic reticulum from rabbit skeletal muscle was investigated using both tension recording from skinned fibres and electrophysiological recording of unitary channel currents from planar lipid membranes. BSA had no effect on the Ca2+ affinity of the contractile proteins, elicited no tension per se in Ca(2+)-loaded skinned fibres, but potentiated caffeine-induced tension. Maximum potentiation was observed with 0.05-0.5% BSA. BSA (0.1%) had no detectable effect on the basal activity of the Ca(2+)-release channel incorporated in lipid bilayer. However, channel stimulation elicited by either caffeine (2 mM) or ATP (60 microM) was further enhanced by BSA (0.1%), as indicated by significant increases in Po, the open probability of the channel. These results suggest that BSA can modulate the response of the skeletal muscle SR Ca(2+)-release channel to different activators such as caffeine and ATP.

Adenosine Triphosphate↗
PubMed1997

Bovine serum albumin potentiates caffeine- or ATP-induced tension in human skinned skeletal muscle fibers.

Human skinned muscle fibers were used to investigate the effects of bovine serum albumin (BSA) on the tension/pCa relationship and on the functional properties of the Ca(2+)-release channel of the sarcoplasmic reticulum (SR). In both fast- and slow-type fibers, identified by their tension response to pSr 5.0, BSA (0.7-15 microM) had no effect on the Ca2+ affinity of the contractile proteins and elicited no tension per se in Ca(2+)-loaded fibers. In contrast, BSA (> 1.0 microM) potentiated the caffeine-induced tension in Ca(2+)-loaded fibers, this effect being more intense in slow-type fibers. Thus, BSA reduced the threshold caffeine concentration required for eliciting detectable tension, and increased the amplitude, the rate of rise and the area under the curve of caffeine-induced tension. BSA also potentiated the tension elicited in Ca(2+)-loaded fibers by low-Mg2+ solutions containing 1.0 mM free ATP. These results suggest that BSA modulates the response of the human skeletal muscle SR Ca(2+)-release channel to activators such as caffeine and ATP.

Adenosine Triphosphate↗
PubMed1996

Effects of the K+ channel blockers paspalitrem-C and paxilline on mammalian smooth muscle.

The tremorgenic alkaloids, paxilline and paspalitrem-C (0.1-10 microM), increased the spontaneous contractility of guinea-pig and rat urinary bladder, and rat duodenum, and induced tension in guinea-pig trachea. These effects are ascribed to blockade of high-conductance, Ca(2+)-activated K+ (BKCa) channels. Paxilline potentiated the charybdotoxin-induced stimulation of guinea-pig detrusor muscle; this is consistent with the alkaloid's ability to allosterically enhance the binding of charybdotoxin to smooth muscle membranes (Knaus et al., 1994). Paspalitrem-C and paxilline did not affect the myogenic activity of isolated portal vein from guinea-pig, which is insensitive to charybdotoxin, or of that from rat which is stimulated by charybdotoxin. Paxilline and paspalitrem-C also differed from charybdotoxin in that the alkaloids did not consistently elicit tension in guinea-pig aortic rings. These discrepancies are attributed to differences in relative potency, sites and/or mechanisms of action of the indole alkaloids vs. peptidyl blockers of the BKCa channel.

Animals↗
PubMed1995

Effects of uridine triphosphate on skinned skeletal muscle fibers of the rat.

Chemically skinned muscle fibers from rat extensor digitorum longus muscle were used to study the effects of uridine triphosphate (UTP) on Ca2+ uptake and release by the sarcoplasmic reticulum (SR) and on Ca2+-activated tensions. Total replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) increased submaximal Ca2+-induced tension (pCa 6.2-5.8) but diminished Po, the maximum tension elicited by pCa 4.2, by ca. 15%, (ii) markedly reduced Ca2+ uptake by the SR (evaluated by caffeine-elicited tension); and (iii) induced tension in Ca2+-loaded fibers. The UTP-induced tension averaged 55% of Po and its rates of development and decay were considerably slower than those of caffeine-evoked tension. The UTP-induced tension (i) depended on the Ca2+-loading conditions; (ii) was reversibly blocked by brief (15 s) exposures of Ca2+-loaded fibers to 5 mM EGTA or by pretreatment with caffeine; (iii) was abolished by functional disruption of the SR with the nonionic detergent Brij-58; and (iv) persisted after blockade of the SR Ca2+ release channels with ruthenium red. Exposure of Ca2+-loaded fibers to UTP depressed the tension elicited subsequently by caffeine, and enhanced the rate of depletion of caffeine-sensitive Ca2+ stores during soaking in relaxing solutions containing 5 mM EGTA. The UTP-induced tension is attributed to increased release of Ca2+ from the SR, via a ruthenium red insensitive pathway(s), combined with reduced Ca2+ uptake by the SR and increased Ca2+ affinity of the contractile proteins.

Adenosine Triphosphate↗
PubMed1994

Inhibition of the myotoxic and hemorrhagic activities of crotalid venoms by Eclipta prostrata (Asteraceae) extracts and constituents.

The antimyotoxic and antihemorrhagic effects of Eclipta prostrata (EP) and three of its constituents (wedelolactone, WE; stigmaterol, ST; and sitosterol, SI) were investigated. The myotoxicity of crotalid venoms (Bothrops jararaca, Bothrops jararacussu and Lachesis muta), purified myotoxins (bothropstoxin, BthTX; bothropasin; and crotoxin), and polylysine was quantified in vitro by the release rate of creatine kinase (CK) from rat or mouse extensor digitorum muscles, and in vivo by the plasma CK activity in mice. The in vitro myotoxicity of the crotalid venoms and myotoxins was neutralized by simultaneous exposure of the muscles to an aqueous extract of EP or to WE. ST and SI were less effective than WE, but interacted synergistically with it. Both the EP extract and WE failed to neutralize the in vitro myotoxic effects of polylysine. The in vivo myotoxicity of venoms and myotoxins was neutralized by their preincubation with the EP extract or WE. Intravenous administration of the plant extract or WE attenuated the increase in plasma CK activity induced by subsequent intramuscular injections of the crotalid venoms or the myotoxins. EP and WE inhibited the hemorrhagic effect of B. jararaca venom, as well as the phospholipase A2 activity of crotoxin and the proteolytic activity of B. jararaca venom. The data provide direct evidence for antimyotoxic and antihemorrhagic effects of EP and WE against the crotalid venoms responsible for most cases of envenomation by snakebites in Brazil. These effects are interpreted as consequences of antiproteolytic and antiphospholipase A2 activities of EP and its constituents.

Animals↗
PubMed1994

A comparison of the effects of UTP and ATP on the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum.

Heavy sarcoplasmic reticulum (SR) membrane fractions from rabbit and porcine skeletal muscle were incorporated into planar lipid bilayers and the activity of the Ca2+ release channels was recorded under voltage clamp, using Cs+ as the current carrier. The effects of the nucleotides adenosine triphosphate (ATP) and uridine triphosphate (UTP) on channel activity were studied at a holding potential of +30 mV. UTP (0.1-1.0 mM) had no effect per se on the conductance or the gating properties of the Ca2+ release channels. In contrast, ATP (> 0.1 mM) increased P(o), the open channel probability, and both tau o1 and tau o2, the open time constants, and decreased tau c1 and tau c2, the closed time constants. The Ca2+ channel conductance, however, was not affected by ATP. Ruthenium red (1-2 microM), a well-known inhibitor of the SR Ca2+ release channel, abolished the ATP-induced channel activation. These electrophysiological data provide support for our contention (G. Suarez-Kurtz et al. (1993). Anais da Academia Brasileira de Ciências, 65:330) that the UTP-induced tension in mammalian "skinned" muscle fibers is not due to stimulated release of SR-stored Ca2+ via the release channel.

Adenosine Triphosphate↗
PubMed1993

Mobilization of intracellular calcium in cultured vascular smooth muscle cells by uridine triphosphate and the calcium ionophore A23187.

The known action of uridine triphosphate (UTP) to contract some types of vascular smooth muscle, and the present finding that it is more potent than adenosine triphosphate in eliciting an increase in cytosolic Ca2+ concentration in aortic smooth muscle, led us to investigate the mode of action of this nucleotide. With this aim, cultured bovine aorta cells were subjected to patch-clamp methodologies under various conditions. Nucleotide-induced variations in cytosolic Ca2+ were monitored by using single channel recordings of the high conductance Ca(2+)-activated K+ (Maxi-K) channel within on-cell patches as a reporter, and whole-cell currents were measured following perforation of the patch. In cells bathed in Na(+)-saline, UTP (> 30 nM) induced an inward current, and both Maxi-K channel activity and unitary current amplitude of the Maxi-K channel transiently increased. Repetitive exposures elicited similar responses when 5 to 10 min wash intervals were allowed between challenges of nucleotide. Oscillations in channel activity, but not oscillation in current amplitude were frequently observed with UTP levels > 0.1 microM. Cells bathed in K+ saline (150 mM) were less sensitive to UTP (approximately 5-fold), and did not show an increase in unitary Maxi-K current amplitude. Since the increase in amplitude occurs due to depolarization of the cell membrane, a change in amplitude was not observed in cells previously depolarized with K+ saline. The enhancement of Maxi-K channel activity in the presence of UTP was not diminished by Ca2+ entry blockers or by removal of extracellular Ca2+. However, in the latter case, repetitive responses progressively declined. These observations, as well as data comparing the action of low concentrations of Ca2+ ionophores (< 5 microM) to that of UTP indicate that both agents elevate cytosolic Ca2+ by mobilization of this ion from intracellular pools. However, the Ca2+ ionophore did not cause membrane depolarization, and thus did not change unitary current amplitude. The effect of UTP on Maxi-K channel activity and current amplitude was blocked by pertussis toxin and by phorbol 12-myristate 13-acetate (PMA), but was not modified by okadaic acid, or by inhibitors of protein kinase C (PKC). Our data support a model in which a pyrimidinergic receptor is coupled to a G protein, and this interaction mediates release of Ca2+ from intracellular pools, presumably via the phosphatidyl inositol pathway. This also results in activation of membrane channels that give rise to an inward current and depolarization. Ultimately, smooth muscle contraction ensues.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1993

Antagonism of the myotoxic effects of Bothrops jararacussu venom and bothropstoxin by polyanions.

The effects of heparin and other polyanions on the myotoxicity of Bothrops jararacussu venom and purified bothropstoxin (BthTX) were investigated. The release rate of creatine kinase (CK) from isolated extensor digitorum longus muscle and the plasma CK activity of mice were used to quantify the results. The myotoxic effects of B. jararacussu venom or BthTX were inhibited by preincubation of these agents with one of the following: a heterogeneous heparin preparation (designated 'heparin'), low mol. wt heparin (H-4500) or dextran sulfates (DS-8000 and DS-500,000). Non-sulfated dextran (D-40,000) and two chondroitin sulfates were ineffective. The antimyotoxic effects of the polyanions are ascribed to their forming inactive acid-base complexes with the basic myotoxins of Bothrops venoms. Gel-filtration experiments in Sephadex provided direct evidence for complex formation between heparin and BthTX. Intravenous (i.v.) administration of H-4500 or DS-8000 opposed the increase in plasma CK activity induced by a subsequent i.m. injection of venom or BthTX. In contrast, pretreatment with i.v. heparin or DS-500,000 enhanced the venom-induced increase in plasma CK activity. This effect was not observed (1) when the animals were treated with a polyvalent antivenom, which inhibits the coagulation and local stasis induced by Bothrops venoms, and (2) when BthTX, which has no thrombotic or hemorrhagic properties, was the myotoxic agent. The potentiation of the venom-induced increase in plasma CK activity by heparin and DS-500,000 is ascribed to improved washout of the CK released from damaged fibers, because of the anticoagulant properties of the drugs.

Animals↗
PubMed1992

Effects of phenytoin on the ventricular tachyarrhythmias of chronic Chagas' disease.

The effects of phenytoin on the ventricular tachyarrhythmias of 11 patients with chronic chagasic myocarditis were investigated, and correlated with the serum phenytoin levels. Physical examination, laboratory tests and 24- to 48-h ambulatory electrocardiographic recordings were performed before, during (7-14 days) and after treatment with phenytoin (4-6 mg/kg/day, orally, in three divided doses). Significant (greater than 90%) reduction of couplets, bigeminy and runs of ventricular tachycardia were observed in 50-67% of the patients, whereas the frequency of isolated premature ventricular contractions was significantly (greater than 70%) reduced in only 2 patients (18%). Proarrhythmic activity was not observed and adverse side effects were of mild intensity and usually transient, except in one patient, who developed pruritus and skin rash in the presence of toxic phenytoin serum levels (27 micrograms/ml). It is suggested that phenytoin may be useful for the control of repetitive forms of ventricular tachyarrhythmias in selected patients with chronic chagasic myocarditis.

Adult↗
PubMed1992

Comparative pharmacokinetics of different oral nifedipine preparations in healthy Brazilian volunteers.

1. The pharmacokinetics of different pharmaceutical preparations of oral nifedipine--Adalat (capsule), Oxcord and Cardalin (tablets)--was determined after administration of single oral doses of 10 mg to nine healthy young Brazilian volunteers (7 men). 2. There were no significant changes in heart rate or systolic and diastolic blood pressure measured in the sitting position within 8 h of nifedipine administration to these normotensive volunteers. No side effects were reported by the volunteers or observed by the attending physicians during the study. 3. No significant differences were observed among the three preparations in relation to the following pharmacokinetic parameters obtained from the plasma concentration-time curves: area under the curve (AUC), slope (beta) and half-life (T1/2) of the elimination phase, volume of distribution (Vd/F) and total body clearance (CL/F), both expressed as functions of the oral bioavailability (F) of nifedipine. 4. The peak plasma concentration of nifedipine (Cmax) and the time to reach Cmax (Tmax) were not different for the two tablet preparations. However, Cmax was significantly higher, and Tmax was significantly shorter for the capsule. These data indicate that the capsule and the tablet preparations are not bioequivalent.

Administration, Oral↗
PubMed1991

Effects of charybdotoxin and iberiotoxin on the spontaneous motility and tonus of different guinea pig smooth muscle tissues.

Charybdotoxin (ChTX) and iberiotoxin (IbTX), two potent peptidyl blockers of the high conductance Ca(2+)-activated K+ channel (PK,Ca) were used to probe the role of this channel in regulating the contractility of various smooth muscles isolated from the guinea pig. Of the spontaneously contracting tissues that have been investigated, bladder and taenia coli are affected by ChTX, whereas portal vein and uterus are relatively insensitive. In the former two tissues, ChTX (10-100 nM) produces a concentration-dependent increase in contractility, with bladder being most sensitive to action of the toxin. ChTX also causes a contracture of quiescent aortic rings, although not affecting indomethacin-treated trachea. In order to demonstrate that the effects of ChTX are due specifically to blockage of PK,Ca, rather than to inhibition of some other K+ channel, two other inhibitors of PK,Ca were monitored. IbTX (10-100 nM), a selective inhibitor of PK,Ca, and tetraethylammonium ion, which blocks PK,Ca at low (0.1-3 mM) concentrations, both increase the myogenic activity of bladder, but not portal vein. In addition, IbTX causes a sustained contracture of aorta. Taken together, these data indicate that the increased contractility of certain guinea pig smooth muscles produced by ChTX, IbTX and tetraethylammonium ion is the result of selective inhibition of PK,Ca. It is suggested that in spontaneously active bladder and taenia coli, PK,Ca provides a repolarization pathway after tissue depolarization, whereas in quiescent aorta, PK,Ca maintains cellular resting potential. In contrast, in indomethacin-treated trachealis muscle, ChTX-sensitive K+ channel pathways are not involved in controlling resting tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Amiloride analogs inhibit L-type calcium channels and display calcium entry blocker activity.

Three structural classes of commonly used amiloride analogs, molecules derivatized at the terminal guanidino-nitrogen, the five-position pyrazinoyl-nitrogen, or di-substituted at both of these positions, inhibit binding of the L-type Ca2+ channel modulators diltiazem, gallopamil, and nitrendipine to porcine cardiac sarcolemmal membrane vesicles. The rank order of inhibitory potencies among the various derivatives tested is well defined with amiloride being the least potent. Saturation binding studies indicate that inhibition of ligand binding results primarily from effects on Kd. Ligand dissociation measurements suggest that amiloride derivatives do not associate directly at any of the known sites in the Ca2+ entry blocker receptor complex. In addition, these compounds do not compete at the "Ca2+ coordination site" within the channel. However, studies with inorganic and substituted diphenylbutylpiperidine Ca2+ entry blockers reveal that amiloride analogs interact at a site on the channel where metal ions bind and occlude the pore. Photolysis experiments performed with amiloride photoaffinity reagents confirm that a specific interaction occurs between such probes and the channel protein. Upon photolysis, these agents produce concentration- and time-dependent irreversible inactivation of Ca2+ entry blocker binding activities, which can be protected against by either verapamil or diltiazem. 45Ca2+ flux and voltage-clamp experiments performed with GH3 anterior pituitary cells demonstrate that amiloride-like compounds inhibit L-type Ca2+ channels directly. Moreover, these compounds block contraction of isolated vascular tissue in pharmacological assays. Electrophysiological experiments indicate that they also inhibit T-type Ca2+ channels in GH3 cells. Taken together, these results demonstrate unequivocally that amiloride analogs display significant Ca2+ entry blocker activity in both ligand binding and functional assays. This property, therefore, can seriously complicate the interpretation of many in vitro and in vivo studies where amiloride analogs are used to elicit inhibition of other transport systems (e.g. Na-Ca and Na-H exchange).

Amiloride↗
PubMed1990

Halothane cooling contractures of skinned mammalian muscle fibers.

The effects of halothane or cooling on Ca2(+)-activated tensions and on the uptake and release of Ca2+ by the sarcoplasmic reticulum were investigated in chemically skinned fibers of the extensor digitorum longus muscle of adult rabbits. At 22 degrees C, halothane (greater than 0.46 mM) induced Ca2+ release from the SR of Ca2(+)-loaded skinned fibers that resulted in transient tensions. Higher concentrations of halothane (greater than 4.65 mM) reduced the steady-state accumulation of Ca2+ in the SR at 22 degrees C. Cooling (to less than 10 degrees C) elicited transient contractures (cooling-induced contractures [CC]) in Ca2(+)-loaded skinned fibers, despite the fact that the tensions elicited by adding Ca2+ to the bath were depressed at these low temperatures. The skinned fibers did not develop CCs at 12-16 degrees C. Halothane cooling contractures could be elicited at these temperatures by exposing the fibers to halothane concentrations that failed to elicit Ca2+ release at 22 degrees C. The halothane cooling contractures were blocked by procaine but not by lidocaine. It was concluded that these contractures resulted from a synergistic interaction between halothane and cooling that stimulates Ca2+ release from, and reduces Ca2+ uptake by, the sarcoplasmic reticulum.

Action Potentials↗
PubMed1990

Potentiation of the halothane-cooling contractures of mammalian muscles by denervation.

Denervation potentiated the cooling-induced contractures and the halothane-cooling contractures of isolated extensor digitorum longus and soleus muscles of the mouse. These effects were more striking in extensor digitorum longus than in soleus muscles. Significant increases in the peak amplitudes of the halothane-cooling contractures of both muscles and of the cooling contractures of soleus muscle were observed within 2 and 7 days of denervation. The potentiation of the contractures persisted for 90 days, the period of this study. Denervation (greater than 2 days) endowed extensor digitorum longus with the ability to generate cooling contractures in the absence of halothane. The rate of tension development of cooling-induced contractures in the absence or presence of halothane was significantly greater in denervated (2-90 days) than in innervated muscles. Denervation also reduced the effectiveness of procaine in inhibiting the halothane-cooling contractures. It is proposed that the potentiation of cooling-induced contractures in denervated muscles results primarily from an increase in the rate of efflux and in the quantity of Ca2+ released from the sarcoplasmic reticulum, upon cooling and (or) when challenged with halothane.

Animals↗
PubMed1990

Alterations in the functional properties of skinned fibers from denervated rabbit skeletal muscle.

Isometric tension was recorded in vitro from chemically skinned fibers obtained from normal and 14-day-denervated extensor digitorum longus muscles of the rabbit. Denervation potentiated the tensions elicited by pCa 6.0 but did not modify the pCa value (5.6) required for maximum tension. Ca2+ transport across the membranes of the sarcoplasmic reticulum (SR) was markedly affected by denervation. Thus the rate of ATP-dependent net Ca2+ uptake increased significantly, and the spontaneous release ("leakage") of the Ca2+ stored in the SR was significantly reduced in denervated fibers. These effects lead to increased accumulation of Ca2+ in the lumen of the SR. The dose-response curve for the halothane-induced contractures of Ca2(+)-loaded skinned fibers was displaced to the left after denervation. Thus 0.7 mM halothane, a concentration that elicited no tension in 10 control fibers, induced contractures in the 10 denervated fibers tested. The potentiation of the halothane-induced tensions is attributed mainly to the larger stores of Ca2+ in the SR of denervated fibers. The possibility that denervation may also affect the interaction of halothane with the SR membranes is discussed.

Adenosine Triphosphate↗
PubMed1990

Pharmacokinetics of oral ciprofloxacin in healthy, young Brazilian subjects.

1. The pharmacokinetics of ciprofloxacin were determined in 8 healthy young volunteers (5 men and 3 women) after administration of single oral doses of 250 mg. 2. The peak plasma concentration of ciprofloxacin (Cmax = 1.26 +/- 0.21 mg/l), the time to reach Cmax (Tmax = 1.99 +/- 0.26 h), the area under the time-plasma concentration curve (AUC = 5.52 +/- 0.84 mg h l-1), the terminal phase half-life (T1/2 = 3.05 +/- 0.56 h), the volume of distribution (Vd/F = 195.4 +/- 14.0 l) and total body clearance (CL/F = 46.3 +/- 2.6 l/h), both expressed as functions of the oral bioavailability (F) of ciprofloxacin were within the corresponding values reported in the literature for other healthy population groups. 3. Multiple dose administration (250 mg, po, twice daily for 4 days) did not result in accumulation of ciprofloxacin in plasma. No adverse side effects occurred during the study. 4. The pharmacokinetic data are discussed in relation to the minimum inhibitory concentration (MIC) of ciprofloxacin for a number of common pathogens isolated from human infections in Rio de Janeiro.

Administration, Oral↗
PubMed1989

Neutralization of lethal and myotoxic activities of South American rattlesnake venom by extracts and constituents of the plant Eclipta prostrata (Asteraceae).

Ethanolic extracts of the aerial parts of Eclipta prostrata L. (Asteraceae) neutralized the lethal activity of the venom of South American rattlesnake (Crotalus durissus terrificus) when mixed in vitro before i.p. injection into adult Swiss mice. Samples of ethanolic extract corresponding to 1.8 mg of dry extract per animal neutralized up to four lethal doses of the venom (LD50 = 0.08 micrograms venom/g animal). Three substances isolated from the plant--wedelolactone (0.54 mg/animal), sitosterol (2.3 mg/animal) and stigmasterol (2.3 mg/animal)--were able to neutralize three lethal doses of the venom. Aqueous extracts of the plant inhibited the release of creatine kinase from isolated rat muscle exposed to the crude venom. The protection conferred against the myotoxic effects of the venom could be demonstrated also in vivo, when the venom was preincubated with the extract prior to injection into mice.

Animals↗