Effects Of Procaine Research Articles

Effects of Procaine On the Development, Longevity and Fecundity of Caenorhabditis Elegans

In medium containing 20 mg/ml of procaine-HCl, juvenile development of Caenorhabditis elegans almost ceased, and juveniles entered a dauer-like state. After transfer to procaine-free medium, the nematodes resumed growth and matured in about 4 days. After transfer to drug-free medium the fecundity of the treated nematodes was markedly reduced even by a one-day exposure to the drug, and unlike longevity the decline proceeded stepwise. Procaine-treated nematodes resisted desiccation less but resisted freezing as did juveniles in the dauer state from monoxenic cultures. Under the electron microscope procaine-treated juveniles had empty intestinal lumens but unlike dauer juveniles the morphology of this region had a thin cuticle and no lateral alae.

Effects of phenetyl alcohol and procaine on the syntheses of cellular arylsulfatase and tyramine oxidase in Klebsiella aerogenes.

β-Phenetyl alcohol and procaine hydrochloride are known to alter membrane structure. Their effects on the syntheses of tyramine oxidase and arylsulfatase were studied in Klebsiella aerogenes. β-Phenetyl alcohol inhibited the syntheses of membrane-bound tyramine oxidase and arylsulfatase, located in the periplasm, under non-repressing and derepressing conditions, but did not affect the syntheses of β-galactosidase and histidase, which are located internally. In contrast, procaine hydrochloride stimulated the synthesis of tyramine oxidase and derepressed the synthesis of arylsulfatase, but inhibited non-repressed synthesis of arylsulfatase. Thus, derepressed synthesis of cellular arylsulfatase was affected by the level of tyramine oxidase synthesis. Structural alterations in the cell membrane seem to impair the formation of active-arylsulfatase protein in the periplasmic space.

Effect of lidocaine and procaine on the action potential of canine sinus nodal cells.

Effects of local anesthetics (lidocaine and procaine) on the canine sinus node were studied using isolated right atrial preparations which were obtained from puppies adn perfused with oxygenated Tyrode solution through the dorsal right atrial artery. Action potential of the sinus nodal area which was characterized by the slow rate of phase O and diastolic depolarization, was recorded using the conventional microelectrode technique, simultaneously with atrial contraction. Lidocaine (10-300 micrograms) prolonged the cycle length and duration of action potential, decreased the rate of phase 4 depolarization and amplitude of action potential, and shifted the threshold potential and maximal diastolic potential to the depolarizing direction. The atrial contraction decreased simultaneously. In higher doses, sinoatrial block was occasionally observed in 8 of 55 experiments. Procaine (10-300 micrograms) had similar negative chronotropic and inotropic effects and induced sinoatrial block in 7 of 57 experiments, but unlike lidocaine, procaine produced positive chronotropic and inotropic effects following the initial negative responses in 16 of 57 experiments. The sinus node acceleration was accompanied by an increase in the rate of phase 4 depolarization. Chronotropic changes of the sinus nodal cells by these drugs were accompanied by the changes in both the rate of phase 4 depolarization and duration of the action potential.

COMPARISON OF THE CHRONOTROPIC RESPONSES TO LOCAL ANESTHETICS (PROCAINE, LIDOCAINE, PRILOCAINE, MEPIVACAINE AND BUPIVACAINE) OF THE CANINE SINUS NODE IN SITU

AbstractEffects of local anesthetics (procaine, lidocaine, prilocaine, mepivacaine and bupivacaine) on the sinus node of the nerve-intact dog heart were studied in situ by means of selective perfusion of the sinus node through the sinus node artery. The agents caused a dose-dependent decrease in heart rate and the order of their potency in decreasing the heart rate was as follows, bupivacaine>lidocaine=mepivacaine=prilocaine>procaine. The decrease in heart rate produced by these local anesthetics was not affected by prior administration of atropine. With procaine and prilocaine, the decrease in heart rate was followed by an increase which was inhibited by propranolol given into the sinus node artery or was suppressed in reserpine-pretreated dogs. Tetrodotoxin also prevented the positive chronotropic effect of procaine. From these results the following conclusion can be drawn: the negative chronotropic effects of these agents are induced mainly by a direct inhibitory action on the sinus node, and partly by blockade of sympathetic tone, and the interaction with the postganglionic adrenergic nerves plays an important role in the induction of the positive chronotropic responses to procaine and prilocaine.

Effect of procaine in crystalloid and blood potassium cardioplegia solutions

This study was undertaken to examine the effects of procaine (P) (2 g/liter) in multidose crystalloid (KCP) and blood (BCP) potassium (25 meq/liter) cardioplegia solutions during 2 hr of hypothermic (22°C) aortic occlusion. Four groups were studied: Group I KCP, P(−) n = 8, Group II KCP, P(+) ( n = 8), Group III BCP, P(−) n = 6, Group IV BCP P(+) n = 8. Change in left ventricular (LV) function was defined as percentage change in center of mass between pre- and postarrest function curves. Regional myocardial flow was measured with microspheres and myocardial metabolism monitored by lactate and oxygen utilization. Ventricular biopsies were serially obtained for myocardial ATP, creatine phosphate, calcium, water content, and ultrastructure study. LV function percentage recovery was 62 ± 4% in Group I, 79 ± 5% in Group II, 81 ± 4% in Group III and 72 ± 4% in Group IV. Myocardial regional flow did not show significant differences between groups P(−) and P(+) though KCP and BCP groups showed different patterns of reperfusion. Lactate and oxygen utilization did not show significant differences between groups. In all groups ATP and calcium were well preserved and mild edema formation was observed at reperfusion. Ultrastructural preservation was good except in Group I where myofilament breakdown was present. Procaine was effective in obtaining spontaneous recovery of normal electrical activity. In conclusion, BCP without procaine significantly improved myocardial protection over similar KCP. Procaine had a significant additive effect in KCP and no additive effect in BCP.

Local anesthetics and the role of sodium in the force development by canine ventricular muscle and purkinje fibers.

We studied the effects of the local anesthetics, procaine and benzocaine, on the action potential and force of canine ventricular muscle and Purkinje fibers. In ventricular muscle, procaine often shifted the plateau to a more positive value and increased the force of contraction, whereas benzocaine shortened the action potential and decreased contractile force. In Purkinje fibers, both local anesthetics reduced contractile force and decreased the duration of the action potential markedly. In ventricular muscle fibers norepinephrine potentiated the positive inotropic effect of procaine and changed the effects of benzocaine from a negative to a positive inotropic effect. The potentiating effect of procaine on contraction was eliminated by propranolol. In the presence of norepinephrine (and the absence of propranolol), in Purkinje fibers both anesthetics decreased force but less than in the absence of norepinephrine. In the presence of tetrodotoxin (TTX) and norepinephrine, procaine and benzocaine increased contractile force of muscle fibers. Under the same conditions in Purkinje fibers, procaine increased contractile force and benzocaine decreased it (but less than in the absence of TTX). Administration of veratridine increased contractile force in both ventricular muscle and Purkinje fibers: under these conditions, both local anesthetics decreased contractile force in both tissues. We conclude that: (1) the positive inotropic effects of procaine and benzocaine are mediated through an adrenergic mechanism; (2) the negative inotropic effect is at least in part mediated through a reduction of sodium influx; and (3) the negative inotropic effect is more pronounced in Purkinje fibers because of a larger steady state sodium influx during the plateau.

Effects of tertiary amine local anesthetics on the assembly and disassembly of brain microtubules in vitro.

From kinetic and electron microscopy studies on the effects of procaine, tetracaine and dibucaine on the polymerization and depolymerization of the microtubules isolated from pig and rat brains the following results were obtained. 1. Procaine or tetracaine, at the concentration range of 0.5--20 mM and of 0.5--5 mM respectively, increases the rate of tubulin polymerization (24 degrees C or 37 degrees C) and of microtubule depolymerization (4 degrees C) as a linear function of the concentration of the anesthetics, while identical amounts of microtubules are formed. In the absence of microtubule-associated proteins the polymerization of tubulin is not induced by 10 mM procaine, furthermore, the critical concentration of microtubule proteins necessary for assembly into microtubules is not affected at this concentration level of the anesthetic. This suggests that procaine affects not the nucleation, but rather the elongation process. 2. Dibucaine, from 0.5 mM to 3 mM increases the lag time of the polymerization reaction, while from 0.5 mM to 2 mM it linearly decreases both tubulin polymerization (24 degrees C) and microtubule depolymerization (4 degrees C) rates. Dibucaine, up to mM concentration, does not affect the extent of tubulin polymerization; however, above this concentration it induces the formation of amorphous aggregates. 3. Procaine or tetracaine enhances the depolymerizing effect of calcium on microtubules. The half-maximal values for the depolymerizing effect of calcium were 0.96, 0.71 and 0.51 mM for the control, in the presence of 10 mM procaine and 5 mM tetracaine respectively.

In vivo effects of local anesthetics on the production of major outer membrane proteins by Escherichia coli

Synthesis of a major outer membrane pore protein (the OmpF protein) by Escherichia coli K-12 was specifically and reversibly inhibited by low doses of procaine and other local anesthetics. The treated cells maintained the same total number of pores in their outer membrane by increased synthesis of the OmpC pore protein. Procaine also inhibited synthesis of the OmpF protein by Salmonella typhimurium and by E. coli B, although in the latter case, some OmpF protein was still detected in the outer membrane of treated cells. Experiments in which transcription was blocked by pretreatment with rifampicin indicated that procaine did not inhibit translation of the stable OmpF mRNA and that there was no pool of preformed OmpF mRNA in cells grown in the presence of procaine. Procaine did not affect biosynthesis of the lipopolysaccharide core and did not inhibit the association of OmpF protein with the peptidoglycan. These results are discussed in terms of the known effects of procaine on membrane molecular packaging.

Interpretation by theoretical model of dynamic and steady components in frog gustatory response.

The behavior of dynamic component (slow component) and steady component of the frog glossopharyngeal nerve response to CaCl2, measured in number of impulses firing per second, was examined under various conditions. 1) The magnitude of the dynamic component increased with the flow rate below about 0.3 ml/s, whereas that of the steady component was independent of the flow rate. 2) The magnitude of the dynamic component increased with a rise of temperature between 2.5 and 20 degrees C, whereas that of the steady component was practically independent of temperature. Removal of Ca2+ from the receptor membrane yielded a large dynamic component even at 2.5 degrees C. 3) The treatment of the tongue with procaine led to a large reduction in the magnitude of the dynamic component, whereas the effect of procaine on the steady component was not pronounced. 4) The magnitude of the dynamic component varied with the pH of the stimulating solution, whereas that of steady component was practically independent of a pH between 4.5 and 7.5. The above results were well interpreted by the following reaction scheme: S (stimulus + A (receptor domain) in equilibrium (SA)active in equilibrium (SA) inactive where (SA) active and (SA) inactive are active and inactive complexes.

164 - Effects of lidocaine and procaine on the action potential of cells in the canine sinus node.

164 - Effects of lidocaine and procaine on the action potential of cells in the canine sinus node.

Actions of 4-aminopyridine on vascular smooth muscle tissues of the guinea-pig.

1 Effects of 4-aminopyridine (4-AP) and procaine on the membrane and contractile properties of smooth muscle cells of the guinea-pig pulmonary artery and portal vein were observed.2 The membrane potential and length constant of smooth muscle cells of the guinea-pig pulmonary artery were -53.2 mV and 1.2 mm, respectively, and those of the portal vein were -52.6 mV and 0.71 mm, respectively. The membrane was electrically quiescent in the pulmonary artery and it was electrically active in the portal vein.3 Both 4-AP and procaine depolarized the membrane, increased the membrane resistance and suppressed the rectifying properties in both tissues. Both agents evoked a graded response from the muscle membranes of the pulmonary artery by outward current pulse. Procaine had a greater effect than 4-AP on the above membrane properties.4 4-AP (10(-5) M) produced contraction without depolarization of the membrane. The contraction evoked by 10(-5) M 4-AP was completely suppressed but that evoked by 5 x 10(-4) M 4-AP was only partly suppressed by phentolamine (10(-7) M). However, the contraction evoked by procaine was not suppressed by phentolamine.5 4-AP enhanced but procaine suppressed the amplitude of 118 mM [K](0)-induced contraction.6 The results suggest that 4-AP and procaine suppress K-conductance of the muscle membrane, and 4-AP but not procaine increases noradrenaline release from the nerve terminal. Presumably intracellular free Ca concentrations are also modified by these agents. The effects of 4-AP and procaine on the vascular muscle were compared with those on other excitable tissues.

Effect of altered membrane lipid composition and procaine on hyperthermic killing of ascites tumor cells.

The influence of membrane fluidity on hyperthermic cell killing has been investigated in ascites tumor cells. Membrane lipid composition of P388 ascites tumor cells were modified by feeding host animals with diets containing either unsaturated fatty acids (UFA) or saturated fatty acids (SFA). Both kinds of ascites were heat treated in vitro at 37, 42 or 43.5 degrees C for 30 or 60 min. The cell killing effect of hyperthermia was tested by transplantation of cells into recipient mice and survival examined. While at 37 and 42 degrees C for 1 h, there was no difference in cell killing of the two types of ascites, elevating the temperature to 43.5 degrees C the survival was significantly longer on transplantation of ascites of UFA diet. This effect was potentiated by membrane-fluidizing drugs. On the addition of 1 mM procaine during 1 h treatment at 43.5 degrees C, the ascites of SFA diet killed 80% of mice, while the ascites of UFA diet left all the mice alive at least for 3 months. Scanning electron-microscopic observations of the treated cells was performed in parallel and showed close correspondence with the results of survival studies. In conclusion, the increase of membrane fluidity by incorporating more of UFA or by the addition of membrane-fluidizing drugs or especially by the combination of both, the sensitivity of cells to heat enhanced. These experiments support the hypothesis that membranes are a target for hyperthermia.

66) - Comparative study of effects of diltiazem, lidocaine, manganese ion, nicardipine, procaine, propranolol, trimetazidine and verapamil on the contraction of isolated guinea-pig vas deferens.

66) - Comparative study of effects of diltiazem, lidocaine, manganese ion, nicardipine, procaine, propranolol, trimetazidine and verapamil on the contraction of isolated guinea-pig vas deferens.

A spin-label study of the effects of drugs on calcium release from isolated sarcoplasmic reticulum vesicles.

The effects of caffeine, thymol, and procaine on calcium release from fragmented sarcoplasmic reticulum (FSR) from rabbit skeletal white muscle were investigated by the spin label method at the organellar level. Two thiol-directed spin labels, 4-maleimide-2,2,6,6-tetramethylpiperidinooxyl and 4-(2-iodoacetamide)-2,2,6,6-tetramethylpiperidinooxyl, were used for the labeling of SR proteins. The ratio (W/S) of the weakly (W) and strongly (S) immobilized ESR signals was measured for the maleimide and iodoacetamide labeled FSR. The two labels gave different W/S values, which means that the two labels report conformational changes at different loci of SR proteins. The dependences of the W/S ratios on the concentration of the drugs showed that conformational changes of SR proteins induced by these drugs are not the same. From measurements of the distribution of 5-doxyldecanoic acid methylester between the lipid and water phases, it was found that the conformational changes of the SR proteins caused by thymol or procaine induced a disorder in local regions of the phospholipid bilayers of FSR, while such disordering was not induced by caffeine. On the other hand, caffeine and thymol showed definite effects on calcium release from FSR, while procaine did not. These results indicate that the effects of the drugs on the protein conformations can be well characterized at the organellar level by means of the spin label technique and that some specific changes in the conformations of SR proteins are necessary for calcium release from FSR.

Cytotoxic effects of procaine, lignocaine and bupivacaine

Cytotoxic effects of procaine, lignocaine and bupivacaine

Procaine-Mediated Modification of Membranes and of the Response to X Irradiation and Hyperthermia in Mammalian Cells

Procaine, a membrane-specific agent, was found to protect the response of oxygenated mammalian cells toward x irradiation in vitro. In addition, the drug also potentiates hyperthermic killing of cells. In an effort to gain further insights into the mechanisms underlying the action of procaine as a modifier of cell injury in x-irradiated and heated cells, the effects of procaine on cellular morphology, membrane fluidity, and cellular electrokinetic properties were studied. It was found that procaine can reversibly influence the cellular morphology. Using scanning electron microscopy, we were able to demonstrate the presence of numerous smooth blebs on the cell surface of either normal or SV40-transformed 3T3 mouse fibroblasts treated with procaine. When 1,6-diphenyl-1,3,5-hexatriene was used as a membrane probe, the overall fluidity of cell membranes from 3T3 cells grown as monolayers or L5178Y lymphoma cells grown in suspensions was not significantly changed by procaine; however, when perylene was used as a probe, the overall fluidity of cell membranes of procaine-treated cells was found to increase significantly. Lastly, procaine was found to alter the electrophoretic mobility of cells. These results indicate that procaine may exert its modification of radiation- and heat-induced effects via a still elusive membrane-mediated mechanism(s). It is anticipatedmore » that membrane-active agents with different specificities may be employed as tools to probe the role of membranes in the radiation or heat response of cells.« less

Local anaesthetic action of the Chinese medicine "Saiko-Keiski-To".

The local anaesthetic action of the Chinese herbal medicine „Saiko–Keishi–To” (SK) and its component crude drugs was examined using the sciatic nerve of the frog. The local anaesthetic action of the 2 % solution of SK extract was 0.29 ± 0.08 times that of 0.5 % procaine solution, and 2 % solutions of extracts of Bupleuri Radix, Cinnamomi Cortex and Zingiberis Rhizoma showed 1.65 + 0.22, 1.66 + 0.13 and 0.73 + 0.20 times the 0.5 % procaine effect respectively.

1‐Methyladenine induction of oocyte (starfish) maturation: Inhibition by procaine and its pH dependency

AbstractFully grown oocytes of starfish (Asterias forbesi) are normally arrested in the dictyate stage of meiosis within the ovary. Reinitiation of meiotic maturation in these oocytes appears to be induced as a result of the interaction of 1‐methyladenine (1‐MA) with the oocyte surface. The objective of this investigation was to determine whether procaine, a membrane active pharmacological agent, alters the ability of 1‐MA to induce oocyte maturation. Procaine (0–2 mM) at pH 8.3 inhibited 1‐MA induced maturation in a dose dependent manner; inhibition of maturation was seen only when the oocytes were incubated with procaine prior to the addition of 1‐MA. The inhibitory effect of procaine was reversible as indicated by the observation that oocytes which failed to mature in seawater containing 1‐MA (1 μg/ml) and 1 or 2 mM procaine at pH 8.3 subsequently underwent maturation after washing the procaine out and incubation with 1‐MA. Procaine inhibition of oocyte maturation was dependent on pH of the seawater; this inhibitory action of procaine decreased as pH decreased from 8.5–6.0. In seawater at pH 7, procaine (2 mM) reduced the biological activity of 1‐MA to approximately 0.1 of its potency; at pH 8.3 procaine completely blocked 1‐MA induction of oocyte maturation. The amount of 1‐MA bound or incorporated into the oocytes, as measured by the radioactivity in oocytes following incubation in seawater containing 3H‐1 methyladenine, is reduced to 10% of control by 2.0 mM procaine. Taken together, the data suggests that procaine inhibits oocyte maturation by limiting the amount of hormone on or in the oocyte and that this effect is pH dependent.

Differential Effect of Procaine on Irradiated Mammalian Cells in Culture

HeLa and V-79 Chinese hamster cells temporarily stored in ampoules were treated with the local anesthetic procaine. Postirradiation treatment increased lethality in HeLa cells depending on drug concentration, duration of treatment and cell density, as measured by colony-forming ability upon plating. If present during irradiation only, procaine protected from irradiation. In V-79 cells procaine potentiated radiation lethality only in freshly trypsinized cells. Procaine effect was thus cell type specific and most likely involved the cell membrane.

EFFECTS OF PROCAINE AND EXTRACELLULAR CALCIUM CONCENTRATION ON RESPONSE OF RAT STOMACH FUNDUS MUSCLE TO ACETYLCHOLINE AND 5‐HYDROXYTRYPTAMINE

1. When rat stomach fundus muscle was incubated for 30 min in Tyrode solution from which calcium chloride had been omitted, there was an almost complete abolition of the contractile response to 5-hydroxytryptamine (5-HT) while that to acetylcholine (ACh) was still present. 2. The maximum tension obtainable with ACh remained the same in external calcium concentrations ranging from 0.45 to 3.6 mM, but the pD2 value increased. 3. A concentration of at least 0.9 mM calcium was needed to maintain a maximum contraction with 5-HT, and the pD2 for this agent also increased significantly with increase in calcium content of the medium. 4. The effects of procaine on the responses of the muscle to 5-HT and ACh were similar to the respective changes induced by lowering the calcium concentration, and were reduced by the addition of calcium. 5. Concentrations of 2.2 x 10(-7) to 3.6 x 10(-5) M procaine reduced the effects of both 5-HT and KCl and suppressed the maximum responses. 6. The maximum responses to KCl and 5-HT were restored at higher concentrations of procaine (greater than 3.6 x 10(-4) M), while the effect of ACh was reduced. 7. It is suggested that 5-HT, like KCl, is almost entirely dependent on extracellular calcium for inducing muscle contraction, while ACh may utilize calcium from bound stores.