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Biomedical subjects

A De Luca

Publications and source records attributed to A De Luca.

At least 19 recordsLinked to original sources
PubMed1992

Chloride channels of skeletal muscle from developing, adult and aged rats are differently affected by enantiomers of 2-(p-chlorophenoxy) propionic acid.

Enantiomers of 2-(p-chlorophenoxy) propionic acid, compounds acting specifically on chloride channels of adult rat skeletal muscles, have been tested on extensor digitorum longus (EDL) muscle of developing and aged rats, in an attempt to characterize the chloride channels responsible for the low chloride conductance (GCl) found in the above physiological situations. The S-(-) enantiomer, which produces a concentration-dependent inhibition of GCl in the adult EDL, is less effective in inhibiting GCl of EDL of either 2-3 weeks or 29 months old rats, particularly at low concentrations. The R-(+) isomer, which in the adult enhances GCl at low concentrations and blocks it at concentrations higher than 10 microM, lacks inhibitory action, enhancing GCl in both developing and aged EDL. At 30-40 days of age both the enantiomers produce almost the same effects exerted in adulthood. From these data we hypothesize that the low GCl found in EDL of developing and aged rats might be due not only to a lower number of conductive channels but also to the presence of a mixed population of isoforms of chloride channels having different pharmacological properties.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1992

Effects of aging on the mechanical threshold of rat skeletal muscle fibers.

Mechanical threshold was measured "in vitro" in extensor digitorum longus (EDL) muscle fibers from rats of 3-4 and 29 months of age, by means of a two microelectrode "point" voltage clamp. The potential needed for evoking a barly visible contraction was determined using depolarizing command pulses of 5-500 ms duration. At each pulse duration, the EDL fibers from aged rats contracted at a significantly more negative potential than did those from the younger adult rats. Accordingly, the strength duration curve of the aged EDL was significantly shifted towards more negative potentials compared to that for adult rats. The rheobase voltages estimated from the fit of such curves were -62.6 +/- 0.81 mV and -57.1 +/- 0.87 mV in aged and adult EDL fibers, respectively. The data suggest that changes in excitation-contraction coupling parallel the prolongation of contractile times observed during aging in mammalian skeletal muscle. These results are consistent with the known reduction in rate and extent of Ca++ uptake by sarcoplasmic reticulum in aged rats.

Aging↗
PubMed1992

Experimental evaluation of the effects of pravastatin on electrophysiological parameters of rat skeletal muscle.

The effects of daily chronic treatment for 6 months with pravastatin was evaluated on the performance of the skeletal muscle system of different rat groups. At all doses (0.1 mg/kg-20 mg/kg) the righting reflex and the electromyographic signals observed in vivo did not show any abnormality. At the end of the treatment the Extensor digitorum longus muscles were dissected from treated and control rats and their passive and active electrical parameters were analyzed in vitro by standard microelectrodes technique. Pravastatin did not modify the chloride conductance nor the excitability characteristics of the fibers. Chronic treatment with pravastatin does not produce any alteration of skeletal muscle function.

Animals↗
PubMed1992

Opposite effects of enantiomers of clofibric acid derivative on rat skeletal muscle chloride conductance: antagonism studies and theoretical modeling of two different receptor site interactions.

The R-(+) enantiomer of 2-(p-chlorophenoxy) propionic acid (CPP) produces a biphasic effect on chloride channel conductance (GCl) of rat skeletal muscle, increasing GCl at low concentrations and decreasing it at concentrations greater than 10 microM; on the other hand, the S-(-) isomer mostly blocks GCl in a concentration-dependent manner. To explain the peculiar behavior of these compounds, a theoretical model based on the presence of two opposing receptor populations controlling chloride channel conductance has been used to fit the experimental data of the concentration-response curves of both S-(-) and R-(+) CPP. An analysis performed by means of the algebraic summation of two logistic terms suggests a reasonable merit of the proposed model and explains the resultant effect of each optical form as follows: S-(-) acts as a full agonist on an inhibitory sites, whereas R-(+) acts as a full agonist at both the inhibitory and excitatory sites. Antagonism studies appear to be consistent with the proposed model. Dose-response curves in which the block of GCl by the S-(-) isomer was evaluated in the presence of the R-(+) isomer (3-10 microM) clearly showed an antagonistic interaction between the two enantiomers, with an increase in the S-(-) concentration for half-maximal block. The antagonism was overcome by high concentrations of S-(-), and this might be consistent with the hypothesis that the block of GCl is modulated by an inhibitory site at which the two enantiomers compete.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1991

Pneumocystis carinii stimulates in vitro production of tumor necrosis factor-alpha by human macrophages.

The ability of Pneumocystis carinii to induce tumor necrosis factor (TNF)-alpha release by monocytes/macrophages from immunocompetent humans was investigated. Monocytes and monocyte-derived macrophages from healthy individuals produced an increased amount of TNF-alpha when exposed to P. carinii cysts obtained from rats with steroid-induced pneumocystosis. The cysts induced increased TNF-alpha production in a dose-dependent manner; baseline TNF-alpha production was restored after addition of an anti-P. carinii hyperimmune serum. Kinetics experiments showed that the secretion of TNF-alpha occurs early and reaches a maximal peak after 8 h. Since TNF-alpha is directly lethal to P. carinii in vitro, it is suggested that the production of this cytokine in response to the cysts may be one of the mechanisms for the control of this parasitic infection.

Adult↗
PubMed1991

Differential sensitivities of avian and mammalian neuromuscular junctions to inhibition of cholinergic transmission by omega-conotoxin GVIA.

Nerve stimulation-induced contractions of the chick biventer cervicis muscle were slowly reduced by omega-conotoxin. However, omega-conotoxin had no effect on skeletal muscle function after i.v. injection in mice or on nerve stimulation-induced contractions of focally innervated muscle of the rat diaphragm or the rabbit proximal oesophagus, or the multiply innervated extra-ocular rectus muscle from rabbit. The lack of effect of omega-conotoxin on mammalian neuromuscular junctions was not due to the high safety factor in transmission or to a high local concentration of Ca2+ originating from the muscle, and could not be accounted for in terms of the operation of facilitatory or inhibitory feedback modulation of transmitter release from motoneurone terminals. It is concluded that the Ca2+ channels of mammalian motoneurone terminals differ from those of avian motoneurone terminals and other omega-conotoxin-sensitive nerve terminals.

Animals↗
PubMed1990

Pharmacological block of chloride channels of developing rat skeletal muscle affects the differentiation of specific contractile properties.

A specific chloride channel blocker, anthracene 9-carboxylic acid was locally applied for 8-9 days on the extensor digitorum longus muscle of 7-8-day-old rats. The effects of chronic anthracene 9-carboxylic acid treatment on muscle development, were evaluated in vitro on the electrical properties with intracellular microelectrodes and in vivo on the contractile parameters by recording isometric concentrations. Our data show that the treatment prevented the normal development of chloride conductance so that by 15 days of age it was 45% lower in fibers of the treated muscles when compared to age-related control fibers. Potassium conductance was not significantly changed by the treatment. In vivo the anthracene-9-carboxylic acid-treated muscles were slower to contract and relax; having a 20% slower time to peak twitch force and time of half relaxation. These muscles were also 32% less fatiguable with respect to the controls. Moreover, in most of the treated muscles tetanic contractions during high-frequency stimulation were not maintained. The block of chloride channels in developing striated fibers appears to affect the differentiation of specific properties of fast skeletal muscle such as the speed of contraction.

Animals↗
PubMed1990

Changes in membrane ionic conductances and excitability characteristics of rat skeletal muscle during aging.

Membrane electrical properties, component ionic conductances and excitability characteristics of extensor digitorum longus muscle from 3-4, 16 and 29 months old rats were measured "in vitro". Fiber diameter, membrane resistance (Rm) and membrane capacitance, increased with aging, and the increase was significant at 29 months. The increase of Rm was mostly due to a decrease of chloride conductance (GC1), whereas potassium conductance (GK) increased only slightly, at 16 and 29 months. Due to the lowered GC1, the latency of action potential increased at both ages with a consequent prolongation of the duration of action potential. Nevertheless, a decrease in the firing capability was recorded in the aged fibers. Our results indicate, that during aging, the most affected parameter of skeletal muscle fibers is GC1, although changes of this passive conductance alone cannot entirely account for the changes in the excitability characteristics recorded.

Aging↗
PubMed1990

Responses of rat isolated intestinal segments to stimulation of perivascular mesenteric nerve fibres.

1. Isolated preparations of segments of rat jejunum were set up for isotonic recording of the activity of the longitudinal smooth muscle and the extrinsic nerve supply running with the mesenteric blood vessels was stimulated for 30-s periods at 0.5-20 Hz. 2. Contractions were regularly elicited during periods of stimulation at 0.5-2 Hz, and were usually elicited during stimulation at 5 Hz, but relaxations were usually elicited during stimulation at 10 and 20 Hz. On cessation of the period of stimulation, a secondary contraction occurred in most preparations regardless of whether the primary response during the period of stimulation had been a contraction or a relaxation. 3. Tetrodotoxin (0.9 microM) abolished responses during periods of stimulation and the secondary contraction. 4. The relaxations were mimicked by noradrenaline and were abolished by blockade of alpha- plus beta-adrenoceptors but were not affected by hexamethonium, indicating that they are attributable to stimulation of postganglionic noradrenergic fibres. 5. The contractions were mimicked by acetylcholine and were abolished by atropine and hexamethonium, suggesting that they are attributable to stimulation of preganglionic cholinergic nerves: they were also abolished in the presence of capsaicin, indicating that sensory neuropeptide-containing nerve fibres may be involved. 6. The secondary contraction that usually occurred on cessation of stimulation was still present after blockade by atropine or capsaicin of the contractions occurring during stimulation. It was also present after blockade by propranolol and phentolamine of the relaxations occurring during stimulation, and was not affected by indomethacin.

Animals↗
PubMed1990

Effects of omega-conotoxin GVIA on autonomic neuroeffector transmission in various tissues.

1. The effects of omega-conotoxin GVIA (conotoxin), a potent inhibitor of neuronal N-type Ca2+ channels, have been examined on responses to stimulation of noradrenergic, cholinergic and non-adrenergic, non-cholinergic (NANC) nerves in a range of isolated tissues to investigate the role of conotoxin-sensitive Ca2+ channels in neurotransmission. 2. Contractions elicited by field stimulation of noradrenergic nerves in rat and mouse anococcygeus muscles, rabbit ear artery and rat vas deferens (epididymal portion) were inhibited by conotoxin. Responses to noradrenaline, and to adenosine triphosphate in the vas deferens, were not affected. 3. Positive chronotropic responses to field stimulation of noradrenergic nerves were inhibited by conotoxin in rat and mouse atria, but responses to noradrenaline and tyramine were not affected. 4. The stimulation-induced release of noradrenaline was inhibited by conotoxin in the rabbit ear artery and in rat and mouse atria. 5. Relaxations in response to stimulation of the noradrenergic perivascular mesenteric nerves were reduced or abolished by conotoxin in rat and rabbit jejunum. The response to noradrenaline in rat jejunum was not affected. 6. Contractions elicited by stimulation of cholinergic nerves were inhibited by conotoxin in rat jejunum and mouse ileum (perivascular mesenteric nerves), and in guinea-pig taenia caeci (field stimulation). Responses to acetylcholine in rat jejunum and mouse ileum were not affected. 7. Contractions elicited by stimulation of the cholinergic plus NANC pelvic nerves were inhibited by conotoxin in rabbit colon, and to a lesser extent in guinea-pig colon. The stimulation-induced contraction of the guinea-pig colon was inhibited by conotoxin by a greater proportion in the presence than in the absence of atropine. Responses to acetylcholine were not affected in the rabbit colon but were slightly reduced in the guinea-pig colon. 8. Relaxations in response to field stimulation of NANC nerves were inhibited by conotoxin in guinea-pig taenia caeci and rat gastric fundus strips, and in rat anococcygeus muscle when the tone was raised by guanethidine but not when it was raised by carbachol. The relaxations produced by sodium nitroprusside in the rat gastric fundus and anococcygeus were not affected. 9. Contractions of the rat bladder elicited by stimulation of the peri-urethral nerves, which are NANC- and cholinergically mediated, were relatively insensitive to inhibition by conotoxin. The response were almost completely abolished by tetrodotoxin. 10. The conotoxin-induced inhibitions of responses to nerve stimulation developed slowly and persisted after removal of conotoxin. The responses were almost completely abolished by tetrodotoxin. 10. The conotoxin-induced inhibitions of responses to nerve stimulation developed slowly and persisted after removal of conotoxin. 11. The inhibitory effect of conotoxin was inversely proportional to the frequency of stimulation (in several preparations) and to the Ca2+ concentration in the bathing solution (in rat vas deferens). These observations suggest that the inhibition by conotoxin of the Ca2+ influx required for excitation-secretion coupling in autonomic nerve terminals is not absolute, and can be overcome by repeated stimulation or by raising the Ca2 + concentration.

Animals↗
PubMed1989

The effects of taurine on pharmacologically induced myotonia.

Taurine reduces the excitability of striated muscle fibers by increasing the membrane conductance to chloride ions (GCl). This action was tested on rats made myotonic by drugs that block GCl by different mechanisms. Experiments were made "in vivo" using electromyographic (EMG) recordings and "in vitro" with intracellular microelectrode recordings from extensor digitorum longus muscle fibers. Taurine did not antagonize the myotonic discharges produced in vivo by anthracene-9-carboxylic acid, nor did it restore GCl lowered in vitro by this agent. However, when myotonia was chronically induced by 20,25 diazacholesterol, taurine given chronically in vivo or acutely in vitro antagonized the EMG myotonia as well as the reduced GCl and increased excitability of single fibers. We conclude that taurine acts directly on chloride channels to modify their kinetics. Our findings suggest that further clinical studies on the use of taurine in muscle disease involving abnormal excitability or chloride channel function will be useful.

Animals↗
PubMed1989

Membrane ionic conductances in normal and denervated skeletal muscle of the rat during development.

The development of membrane ionic conductances of rat extensor digitorum longus (EDL) muscle fibers was studied in vitro using intracellular recordings. At 7-8 days after birth, the potassium conductance (GK) dominated the total membrane conductance while the chloride conductance (GCl) was very low. A rapid increase of GCl towards adult values was observed after few days (12-14 day old rats), whereas GK did not decrease up to day 23. Denervation at 7-8 days after birth suppressed the maturation of the electrical parameters measured, and 15 days after the nerve crush, GCl was just detectable. These results suggest that the maturation of the electrical properties, and in particular that of the resting chloride conductance in mammalian striated muscle fibers, occurs during the first weeks of postnatal life and is dependent on innervation.

Animals↗