Biomedical subjects

O Casis

Publications and source records attributed to O Casis.

25 records · Page 2Linked to original sources

PubMed1993

Effects of lisinopril on electromechanical properties and membrane currents in guinea-pig cardiac preparations.

1. The effects of the angiotensin-converting enzyme inhibitor, lisinopril, were studied in guinea-pig atria and papillary muscles and in single isolated ventricular cells. 2. In isolated right atria, lisinopril (0.001-10 microM) decreased the amplitude and rate of the spontaneous contractions. In electrically driven left atria this negative inotropic effect was accompanied by a shortening of the time to peak tension and time for total contraction. 3. Lisinopril did not modify the electrophysiological characteristics of the ventricular action potentials recorded in papillary muscles perfused with normal Tyrode solution or elicited by isoprenaline in papillary muscles perfused with 27 mM K Tyrode solution. 4. In single ventricular cells, lisinopril (10 microM) had no effect on the inward L-type Ca2+ (ICa,L), the inward rectifier (IK1) or the delayed rectifier K+ currents (IK). However, it abolished the stimulation-dependent facilitation of the L-type Ca2+ current. 6. These results indicate that the negative inotropic effect of lisinopril cannot be explained by a decrease in Ca2+ entry through L-type channels and suggest that lisinopril may possibly act at an intracellular site to reduce contractile force.

Action Potentials↗

PubMed1993

Effects of the novel potassium channel opener, UR-8225, on contractile responses in rat isolated smooth muscle.

1. The effects of UR-8225 [(1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonapht halen-6- carbonitrile)] and levcromakalim were studied on the electrical and contractile responses induced by noradrenaline and KCl and on 86Rb+ efflux in rat aortic rings and on spontaneous mechanical activity in rat portal vein segments. 2. UR-8225 and levcromakalim, 10(-9) M-10(-5) M, relaxed the contractile responses induced by noradrenaline (IC50 = 2.7 +/- 0.4 x 10(-6) M and 6.6 +/- 1.3 x 10(-7) M, respectively) or 30 mM KCl (IC50 = 1.4 +/- 0.2 x 10(-7) M and 9.4 +/- 1.3 x 10(-8) M, respectively) more effectively than those induced by 80 mM KCl. The relaxant effect on noradrenaline-induced contractions was independent of the presence or absence of functional endothelium. 3. The vasorelaxant effect of UR-8225 and levcromakalim can be competitively antagonized by glibenclamide, an ATP-sensitive K+ channel blocker. There were no differences in the calculated pA2 values for glibenclamide to inhibit UR-8225- and levcromakalim-induced relaxations (7.61 +/- 0.08 and 7.69 +/- 0.10, respectively). The slope of the Schild plot yielded values not significantly different from unity (0.95 +/- 0.06 and 0.96 +/- 0.05, respectively). 4. UR-8225 (10(-5) M) hyperpolarized the resting aortic membrane potential from -50.7 +/- 0.7 mV to -66.0 +/- 2.0 mV and stimulated 86Rb+ efflux. 5. UR-8225 and levcromakalim inhibited the contractions induced by Ca2+ in aortae incubated in Ca(2+)-free PSS containing methoxyverapamil in the presence of noradrenaline. 6. Both drugs inhibited the amplitude of spontaneous activity in portal veins (IC50 = 5.1 +/- 1.4 x 10-8 M and 1.5 +/- 0.7 x 10-8 M, respectively), this effect being competitively antagonized by glibenclamide.7. These results indicated that UR-8225 exhibited qualitatively similar, but slightly less potent,vasorelaxant effects than those exerted by levcromakalim, which suggests that they can be related to its ability to activate ATP-sensitive K+ channels in vascular smooth muscle cells.

Animals↗

PubMed1992

Regional distribution of neuropeptide-degrading enzyme activity in the rat brain: effects of subacute exposure to carbon disulfide.

Carbon disulfide, a volatile solvent, is widely used in industry. It has been demonstrated that it causes several neuropsychological symptoms. However, the neurochemical basis of its neurotoxic effect is relatively unknown. In this paper we have measured the effect of subacute i.p. administration on neutral and basic aminopeptidase activities in discrete zones of the rat brain using lysine- and leucine-2-naphthylamides as substrates. Neutral aminopeptidase activity showed a significant decrease in the thalamus and cerebellum with marked (not significant) changes in the hypothalamus, hippocampus, medulla, and occipital cortex. There were no changes in basic aminopeptidase activity. It is suggested that aminopeptidase activity could play a role in carbon disulfide neurotoxic action in the aforementioned regions by generating changes in several neuropeptide levels.

2-Naphthylamine↗

PubMed1992

Effect of subacute benzene exposure on the activity of two neuropeptide-degrading enzymes in the rat brain.

Benzene (Bz) is an important industrial chemical, a petroleum by-product, a component of unleaded gas, and thus a ubiquitous environmental pollutant. It is well established that this organic solvent possesses neurotoxic and behavioral effects. However, the neurochemical mechanism of the solvent action remains obscure. The aminopeptidases (AP) are proteolytic enzymes that have been proposed as a candidate regulator of the degradation of several neuropeptides. In this work, changes in Lys- and Leu-aminopeptidase activities in several rat brain regions after benzene administration are described. The AP activity was determined by measuring the rate of hydrolysis of the artificial substrates Lys- and Leu-2-naphthylamides (fluorimetrically detected in triplicate). Both enzyme activities decrease in the thalamus, hypothalamus, hippocampus, and amygdala after Bz treatment. It is suggested that these aminopeptidase activities play a part in the benzene action mechanism, possibly by regulating the activity of several neuroactive peptides.

Aminopeptidases↗

PubMed1992

Pyroglutamyl [correction of Pyroglutamil] -peptidase I activity in the cortex of the cat brain during development.

Thyrotropin Releasing Hormone (TRH) is a principal regulator of thyroid system function. However, significant concentrations of TRH were found throughout the central nervous system, the cortex being one of the areas most richly endowed with thyroliberin. Research concerning the functional role of this brain peptide is performed, in part, by studying peptidase enzymes which may be involved in the inactivation of the peptide. The pGlu-His bond is cleaved by two pyroGlu-peptidases: I (soluble) and II (membrane-bound). In the present investigation, developmental activity of the soluble form is described in the cortices of the cat brain. The selected maturation stages were 15 and 30 days postnatal. The cortices were the frontal, parietal, area 17 and areas 18 and 19 as a whole, distinguishing brain hemispheres in all cases. PyroGlu-aminopeptidase I activity increased significantly with age in all the brain regions except area 17. It is suggested that this enzyme activity plays a part in the neurochemical changes that take place during brain maturation.

Animals↗

PubMed1992

Effect of phenobarbital administration on the activity of two neuropeptide-degrading enzymes in several brain areas of the rat.

Phenobarbital (CAS 50-06-6) is widely used as an effective anticonvulsant drug. Many attempts have been made to elucidate the neurochemical basis of its therapeutic action, but with little success. In the present paper, research has been focused on analyzing the effect of phenobarbital administration on two neuropeptide-degrading enzymes, the Lys- and Leu-aminopeptidases, in several brain areas of the rat. The study was performed by measuring the rate of hydrolysis of the substrates Lys- and Leu-2-naphthylamides, by neutral and basic aminopeptidase activities, respectively. Significant increases after phenobarbital administration, for both kinds of aminopeptidase activities, in the frontal, parietal and occipital cortices and the hippocampus were observed. It is suggested that these enzymes play a part in the neurochemical mechanism of the barbiturate, possibly by regulating the activity of several neuroactive peptides in the above mentioned cerebral regions.

Aminopeptidases↗

PubMedDate not supplied

Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats.

BACKGROUND: Alpha-adrenergic stimulation regulates cardiac contractility by reducing repolarising K+ currents. Despite this, no published work exists on the effects of norepinephrine on isolated cardiac transient outward current, responsible for action potential duration in the rat and human. Besides, diabetes alters cardiac inotropic responses to sympathetic innervation, and this can result from altered responsiveness of the transient outward current to norepinephrine. METHODS: Transient outward K+ current was measured using the whole-cell configuration of the patch-clamp technique. Myocytes were isolated from the right ventricle of healthy and streptozotocin-induced diabetic rats. RESULTS: Norepinephrine, through alpha(1)-adrenoceptors, reduces current amplitude in a concentration-dependent way, with no effects on current kinetics or voltage dependence of inactivation. Diabetes reduces current amplitude and accelerates its inactivation process. Norepinephrine also reduces current amplitude in diabetic cells; however diabetes shifts to the right the concentration-response curve and reduces the maximum effect of the neurotransmitter. CONCLUSIONS: Norepinephrine reduces the amplitude of isolated ventricular transient outward K+ current with no effects on current properties in myocytes isolated from either healthy or diabetic hearts. Diabetes shifts the concentration-response curve; thus diabetic myocytes are more resistant to sympathetic regulation than are healthy cells.

Adrenergic alpha-Agonists↗