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PubMed1981

Endogenous dopa in rat brain. Occurrence, distribution and relationship to changes i catecholamine synthesis.

Dopa was isolated from rat brain by cation exchange chromatography and determined by a radioenzymatic method using catechol-O-methyl-transferase and [3H]-S-adenosyl-methionine as cofactor. The product [3H]-methoxytyrosine was purified by cation and anion exchange chromatography. For identification of presumed endogenous dopa isolated from rat brain and rat blood plasma the [3H]-labelled product was purified further by thin-layer chromatography. In the brain of rats killed by decapitation, dopa in a concentration of 7 ng/g was identified. When unstressed rats were killed by focussed microwave irradiation at 2.450 MHz and 8 kW for 1.3 s dopa levels as high as 20 ng/g were measured. The regional distribution of dopa in brain or rats killed by microwaves was similar to the distribution of catecholamines, dopa levels being highest in c. striatum and lowest in cerebellum. Inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine methylester HCl, 250 mg/kg i.p. 90 min before death did not change the brain dopa levels in rats killed by decapitation or in rats killed by microwaves. Compounds, such as haloperidol, chlorpromazine, apomorphine and pentobarbital which are known to increase or decrease catecholamine synthesis did not change the basal level of dopa. The data indicate that in rat brain, the main portion of dopa is associated with catecholamine-containing nerve terminals and that this portion is present in a pool which is only slowly metabolized. A second very small pool of dopa must exist, which is serving as precursor pool for catecholamines and which is turned over at a higher rate. It can be concluded that the basal dopa level cannot be used as an indicator of catecholamine synthesis.

Animals↗
PubMed1985

The handling of five catecholamines by the extraneuronal O-methylating system of the rat heart.

In a comparative study, the handling of five catecholamines by the extraneuronal O-methylating system of the rat heart was determined; all rats were pretreated with reserpine, monoamine oxidase and neuronal uptake were inhibited in all experiments. Hearts were perfused for 7 min with a tracer concentration of 3H-(+/-)-isoprenaline, either in the absence or in the presence of unlabelled catecholamines (which reduced the O-methylation of the tracer amine). IC50's were determined for unlabelled catecholamines and then converted to "half-saturating outside concentrations", i.e., to those concentrations in the perfusion fluid that half-saturate the intracellular catechol-O-methyl transferase (COMT). The values for the (-)-isomers of dobutamine, isoprenaline, adrenaline and noradrenaline and that for dopamine were low and rather similar (between 0.67 and 2.7 mumol/l). Stereoselectivity for isoprenaline probably reflected the preference of uptake2 for the (-)-isomer. The effects of (-)- and (+)-dobutamine indicated that both isomers are a) transported by uptake2 and b) good substrates of COMT. The Vmax for O-methylation [determined for 3H-(+/-)-isoprenaline, 3H-(+/-)-adrenaline, 3H-(+/-)-noradrenaline and 3H-dopamine] was rather similar for all four catecholamines. It is concluded that the extraneuronal O-methylating system of the rat heart handles the five catecholamines in a similar manner, although the Km for uptake2 had been found to increase substantially in the order: dobutamine less than isoprenaline less than adrenaline less than noradrenaline less than dopamine (Grohmann and Trendelenburg 1984b).

Animals↗
PubMed1982

Involvement of catecholamines in Haemophilus influenzae induced decrease of beta-adrenoceptor function.

The deeper airways of patients with asthmatic bronchitis are often infected with Haemophilus influenzae. Vaccination of guinea pigs with H. influenzae resulted in a significant impairment of the isoproterenol induced relaxation of isolated tracheal spirals by approximately 50% 4 days following vaccination. In the present study we further investigated the effects of some drugs affecting catecholamine release on the H. influenzae induced functional desensitization of tracheal spirals. Benserazide, an inhibitor of dopa-decarboxylase, completely prevented the reduction in isoproterenol-induced relaxation after H. influenzae vaccination, while no effect on relaxation of tracheal spirals from control animals was detected. On the other hand, inhibiting the re-uptake of catecholamines with desipramine did not influence the relaxation in the H. influenzae vaccinated tracheal spirals. Treatment of control animals with desipramine however resulted in a decreased relaxation of the isolated spirals by 40%. One day following vaccination with H. influenzae the level of norepinephrine in lung tissue was significantly elevated by 71%, and in plasma by 77%, while after 4 days no significant effects were observed. The spontaneous release of norepinephrine, epinephrine and dopamine of tracheal incubates was increased at days 1 and 4 following vaccination. The release of catecholamines from minced lung incubates of H. influenzae pretreated guinea pigs did not differ from that of controls. On the basis of these results it may be suggested that catecholamine metabolism is changed in lungs from H. influenzae vaccinated animals. Catecholamines, accordingly may play a role in the desensitization of beta-adrenoceptors by H. influenzae.

Animals↗
PubMed1995

Physical conditioning in rats influences the central and peripheral catecholamine responses to sustained exercise.

We have investigated the effect of treadmill running in rats (25m.min-1 using a 3% gradient; for 1 h or 2 h) on the cortical extracellular concentrations of noradrenaline (NA) and its main metabolites-3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol- and the plasma adrenaline (A) and NA concentrations in relation to prior physical conditioning (1 or 2-h running.day-1 for 12 days). Cortical microdialysates and peripheral blood were collected during 1-h resting, 1-h or 2-h running and for 1 h after exercise. Catecholamines and their metabolites were quantitated using high performance liquid chromatography with electrochemical detection. Treadmill running stimulated concomitantly peripheral catecholamine secretion and central noradrenergic activity, i.e. NA turnover and release. The effect extended into the recovery period even more as the duration of the run increased. Prior physical conditioning greatly influenced the central and peripheral catecholamine responses: the 1-h trained rats experienced the 2-h run as a stressful new event eliciting great long-lasting catecholamine responses, whereas the 2-h trained rats exhibited a progressive sustained catecholamine increase with an earlier onset of the central NA release. The data are discussed in relation to the psychological and intellectual effects of exercise and physical fitness in humans. In addition, the positive correlation found between the central noradrenergic activation and peripheral A secretion confirmed and extended our previous observations in exercising men and gave support to the hypothesis that the elevation of circulating A can be a relevant factor mediating--directly or indirectly--the exercise-induced central effects.

Animals↗
PubMed1984

In vivo release by histamine agonists and antagonists of endogenous catecholamines in the cat hypothalamus.

The posterior hypothalamus of anaesthetized cats was superfused through a push-pull cannula with histamine agonists and antagonists and the release of endogenous catecholamines was determined in the superfusate. Hypothalamic superfusion with histamine, 2-methylhistamine (H1-agonist), dimaprit (H2-agonist) or metiamide (H2-antagonist) enhanced the release of the catecholamines dopamine, noradrenaline and adrenaline. The releasing effects of these substances depended on the presence of calcium ions. Superfusion with 2-pyridylethylamine (H1-agonist) was virtually ineffective, while superfusion with 2-thiazolethylamine (H1-agonist) enhanced the rates of release of noradrenaline and adrenaline without influencing the release of dopamine. Superfusion with mepyramine (H1-antagonist) inhibited the release of noradrenaline and adrenaline without affecting the release of dopamine. Hypothalamic superfusion with a concentration of procaine which was equi-anaesthetic to that of mepyramine was ineffective. Ranitidine (H2-antagonist) did not alter the rates of release of the catecholamines. The releasing effect of histamine was inhibited on hypothalamic superfusion with mepyramine and ranitidine. Ranitidine also inhibited the releasing effects of dimaprit and 2-methylhistamine thus indicating that the releasing action of the latter compound was mainly due to stimulation of H2-receptors. These data suggest that blockade of H1-receptors of the posterior hypothalamus reduces the release of noradrenaline and adrenaline, while stimulation of H1-receptors seems to increase the rates of release of these two catecholamines. Stimulation of H2-receptors enhances the release of all three catecholamines. Thus, dopaminergic neurones of the hypothalamus seem to possess H2-receptors, while noradrenergic and adrenergic neurones possess H1- and H2-receptors.

Animals↗
PubMed1983

Inhibition by alpha 2-adrenoceptor agonists of the secretion of catecholamines from isolated adrenal medullary cells.

In adrenal medullary cells, carbachol evokes the secretion of catecholamines with simultaneous uptake of 45Ca. Highly selective agonists for alpha 2-adrenoceptors, clonidine, naphazoline, guanfacine, tramazoline and oxymetazoline inhibited carbachol evoked secretion of catecholamines in a dose-dependent manner. These alpha 2-agonists also inhibited the uptake of 45Ca evoked by carbachol with similar dose-response curve to inhibition of catecholamine secretion. On the contrary, highly selective agonists for alpha 1-adrenoceptors, phenylephrine and norfenefrine did not inhibit the secretion of catecholamines and cellular uptake of 45Ca. The inhibition by alpha 2-agonists was not restored either by the increase in carbachol or Ca concentrations, suggesting that the mode of inhibition was distinct from competition at cholinergic receptors or Ca-channels. It is likely that alpha 2-agonists inhibited the secretion of catecholamines via the inhibition of Ca uptake which was probably caused through the activation of alpha 2-adrenoceptors.

Adrenal Medulla↗
PubMed1985

On the mechanism of catecholamine-induced hyperpolarization of skeletal muscle cells.

Catecholamines (noradrenaline, adrenaline and isoprenaline) were tested for their effect on the resting membrane potential of mouse skeletal muscle cells. In freshly isolated muscles incubated in the normal solution containing 5 mol . l-1, catecholamines increased the resting membrane potential (RMP) by 3-5 mV. In Na+-loaded muscles incubated in a K+-free solution, however, catecholamines increased the RMP by 13-16 mV; consequent application of K+ to these muscles did not hyperpolarize the membrane further. A significant decrease of input membrane resistance was observed during the noradrenaline-induced hyperpolarization. This indicates that the passive membrane permeability for K+ ions was apparently increased. Noradrenaline-induced hyperpolarization requires the presence of calcium ions in the incubation solution. We therefore assume that catecholamines hyperpolarize the membrane by Ca2+-dependent K+-channels activation. The action of catecholamines on the resting membrane potential of skeletal muscle exhibits a 50% nonspecific effect as far as the adrenergic receptor is concerned, and the rest may be blocked by adrenergic blocking agents.

Animals↗
PubMed1986

Plasma renin activity, aldosterone and catecholamine levels when swimming and running.

The purpose of this study was to determine the response of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and catecholamines to two graded exercises differing by posture. Seven male subjects (19-25 years) performed successively a running rest on a treadmill and a swimming test in a 50-m swimming pool. Each exercise was increased in severity in 5-min steps with intervals of 1 min. Oxygen consumption, heart rate and blood lactate, measured every 5 min, showed a similar progression in energy expenditure until exhaustion, but there was a shorter time to exhaustion in the last step of the running test. PRA, PAC and catecholamines were increased after both types of exercise. The PRA increase was higher after the running test (20.9 ng AngI X ml-1 X h-1) than after swimming (8.66 ng AngI X ml-1 X h-1). The PAC increase was slightly greater after running (123 pg X ml-1) than swimming (102 pg X ml-1), buth the difference was not significant. Plasma catecholamine was higher after the swimming test. These results suggest that the volume shift induced by the supine position and water pressure during swimming decreased the PRA response. The association after swimming compared to running of a decreased PRA and an enhanced catecholamine response rule out a strict dependence of renin release under the effect of plasma catecholamines and is evidence of the major role of neural pathways for renin secretion during physical exercise.

Adult↗
PubMed1980

Tyrosine loading enhances catecholamine excretion by rats.

Tyrosine administration to rats causes dose-related increases in urinary catecholamine levels without reducing tissue catecholamines. Pretreatment with carbidopa, a peripheral inhibitor of aromatic-L-amino acid decarboxylase, reduces basal urinary catecholamine levels and blocks of urinary catecholamine increases caused by tyrosine administration or cold exposure. DOPA excretion, which is usually undetectable by our methods, becomes significant after carbidopa, and rises a further four-fold when rats are also given tyrosine. These observations suggest that tyrosine availability can affect both catecholamine synthesis in and release from the sympathoadrenal apparatus.

Adrenal Glands↗
PubMed1996

Regulation of N-terminus-deleted human tyrosine hydroxylase type 1 by end products of catecholamine biosynthetic pathway.

The N-terminal 52-, 70-, and 157-amino acids-deleted mutants and wild-type tyrosine hydroxylases were expressed in Escherichia coli and utilized to investigate the roles of the N-terminus in the catecholamine inhibition on enzyme activity. Their lysate's supernatants were used as enzyme samples. Three catecholamines, namely dopamine, norepinephrine, and epinephrine, affected both wild-type and mutant enzymes after preincubation in the mode of mixed inhibition, and the most marked alteration among the kinetic parameters produced by the deletion was the increase in the inhibition constants. The deletions also abolished the catecholamine-induced shift of the pH profile of the enzyme activity toward a more acidic pH optimum. All three mutants responded to catecholamines almost in the same way. These results suggest that the three catecholamine end products exert their inhibition on tyrosine hydroxylase to the same extent and that the N-terminal 52 amino acid residues contain the key sequence in mediating the inhibitory action.

Catalysis↗
PubMed1989

Role of circulating catecholamines in the control of pancreatic polypeptide and gastrin release.

The influence of circulating catecholamines on the release of pancreatic polypeptide (PP) and gastrin was studied in volunteers. Physical exercise increased plasma epinephrine by 374 +/- 123% and plasma norepinephrine by 167 +/- 30%, but plasma PP concentrations remained unchanged during standardized bicycle ergometry. Immediately after cessation of exercise catecholamine levels decreased rapidly, whereas PP concentrations increased by 55%. In a second series, epinephrine infusion (5, 25, and 75 ng.kg-1.min-1) increased epinephrine levels by 38 +/- 12, 331 +/- 69, and 1229 +/- 131%, respectively, whilst norepinephrine was unaffected. Neither during nor after catecholamine infusion PP secretion was affected. Gastrin release increased by a maximum of 85 +/- 38% (at epinephrine 75 ng.kg-1.min-1). It is concluded, that (1) changes in circulating adrenaline do not significantly influence PP secretion in man; (2) the PP increase immediately following physical exercise cannot be attributed to a rapid fall of catecholamine levels; (3) endogenous catecholamines are of minor importance in the control of gastrin secretion.

Adult↗
PubMedDate not supplied

Myocardial catecholamine responsiveness of spontaneously hypertensive rats as influenced by swimming training.

Alterations of myocardial mechanical catecholamine responsiveness by swimming training (2 X 90 min/day, 4 weeks) were examined in 13-week-old spontaneously hypertensive males rats (SHR). The relationships between myocardial mechanical catecholamine responsiveness and ventricular beta-adrenoceptors as well as myosin isoenzyme pattern were also examined. Compared with sedentary controls, trained rats showed a greater responsiveness to isoproterenol (10(-6) mol/l) on isometric tension (T) and its first derivative (dT/dt) (delta T: 0.45 +/- 0.55 vs. -0.15 +/- 0.11 10(-2) N/mm2, p less than 0.01, delta dT/dt: 17.1 +/- 10.1 vs. 8.3 +/- 3.6 10(-2) N/mm2 X s, p less than 0.05). In sedentary SHR, dT/dtmax increased significantly, whereas developed tension decreased slightly, coupled with a decrease of time to peak tension by high dose (10(-6) mol/l) isoproterenol. Therefore, it can be stated that dT/dt is a better indicator for catecholamine sensitivity than isometric tension. beta-adrenoceptor density [( 3H]-dihydroalprenolol binding) decreased significantly in trained rats (68.7 +/- 7.62 vs. 102.4 +/- 4.37 fmol/mg protein, p less than 0.01) with no significant difference in KD values (4.61 +/- 2.26 vs. 6.11 +/- 1.94 nM, ns). In addition, myosin isoenzyme pattern revealed by pyrophosphate gel electrophoresis shifted towards VM-1 after swimming training. The increased catecholamine sensitivity of fast contracting myocardium is, in principle, compatible with the assumption of cAMP-dependent regulation of myofibrillar ATPase activity (21) or cross bridge kinetics (9), although other postreceptor processes should also be taken into consideration for the increased catecholamine sensitivity.

Adenosine Triphosphatases↗
PubMed1980

Contribution of prostaglandin to the contraction induced by catecholamines in the isolated gallbladder of the guinea-pig.

Possible contribution of prostaglandins to the mechanical response produced by catecholamines was investigated in the isolated strips of the guinea-pig gallbladder. The contraction by catecholamine was blocked by an alpha-blocker, phentolamine (10(-6)M and relaxation was blocked by a beta-blocker, propranolol (10(-6)M. The rhythmic spontaneous motility and intrinsic tone were markedly inhibited by a prostaglandin synthesis inhibitor, indomethacin (10(-7)M. Furthermore, exogenous prostaglandins F2 alpha, E1 and E2 produced potent stimulant actions on gallbladder and the order of potency was found to be E2 > E1 > F2 alpha. The contractile response of catecholamines was abolished almost completely by indomethacin (10(-7)M. Even after the muscle tone was elevated by exogenous prostaglandin after treatment with indomethacin, catecholamine produced no contractile response, although it still relaxed the preparation through activation of beta-receptor. Based on these results, it was suggested that endogenous prostaglandins appear to be contributed to the alpha-action of catecholamines in the isolated guinea-pig gallbladder.

Animals↗
PubMed2006

Magnesium in the management of catecholamine-secreting glomus tumours with intracranial extension.

PURPOSE: Catecholamine-secreting glomus jugulare tumours are uncommon and their anesthetic management can be challenging. The authors present the first description of the use of magnesium sulfate in the management of two patients with catecholamine-secreting glomus jugulare tumours where there was significant intracranial extension. CLINICAL FEATURES: Patient 1 underwent a transmastoid transoccipital excision of a catecholamine-secreting glomus tumour. He exhibited marked hemodynamic instability after handling of the tumour began, which was not controlled by sodium nitroprusside. Improved hemodynamic stability was seen after the patient received magnesium sulfate. Patient 2 also underwent a transmastoid transoccipital excision of a catecholamine-secreting glomus tumour. Magnesium sulfate was commenced prior to tumour handling and continued until the tumour was removed. The patient remained hemodynamically stable. Sodium nitroprusside was not required. CONCLUSION: Magnesium sulfate may be useful in preventing or minimizing the blood pressure changes associated with handling during excision of catecholamine-secreting glomus jugulare tumours. It may be of particular benefit in patients where there is significant intracranial extension.

Aged↗
PubMed1997

1,1'-Diisopropyl-2,4'-cyanine (disprocynium24), a potent uptake2 blocker, inhibits the renal excretion of catecholamines.

1,1'-Diisopropyl-2,4'-cyanine (disprocynium24), a potent inhibitor of the extraneuronal monoamine transport system (uptake2), was previously shown to reduce the clearance of catecholamines from plasma not only by blocking uptake2 but presumably also by blocking organic cation transport. To provide more direct evidence for the latter conclusion, the present study was carried out in anaesthetized rabbits. It aimed at determining the effect of disprocynium24 on the renal excretion of catecholamines which is known to be, at least in part, a consequence of organic cation transport in the kidney. To this end, the plasma clearance due to renal excretion (Cl(u)) of endogenous as well as infused 3H-labelled adrenaline, noradrenaline and dopamine was determined for 60-min periods of urine collection in rabbits treated either with disprocynium24 (270 nmol kg(-1) i.v. followed by i.v. infusion of 80 nmol kg(-1) min(-1)) or vehicle. Two groups of animals were studied: group I (monoamine oxidase and catechol-O-methyltransferase intact) and group II (monoamine oxidase and catechol-O-methyltransferase inhibited). A third group of animals with intact monoamine oxidase and catechol-O-methyltransferase was used to study the effect of disprocynium24 on the glomerular filtration rate (as determined by measuring the plasma clearance of inulin). In vehicle controls, Cl(u) of endogenous adrenaline, noradrenaline and dopamine was 7.2, 5.2 and 153.6 ml kg(-1) min(-1), respectively, in group I and 10.4, 7.0 and 134.3 ml kg(-1) min(-1), respectively, in group II. Similar control values of Cl(u) were obtained for infused 3H-adrenaline and 3H-noradrenaline, but not for infused 3H-dopamine; Cl(u) of 3H-dopamine (4.9 ml kg(-1) min(-1) in group I and 15.4 ml kg(-1) min(-1) in group II) was considerably smaller than Cl(u) of endogenous dopamine, indicating that most of the dopamine in urine (i.e., 98% in group I and 92% in group II) was derived from the kidneys rather than from the circulation. By contrast, only about one quarter of the noradrenaline in urine (32% in group I and 24% in group II) and none of the urinary adrenaline were of renal origin. In both groups, disprocynium24 markedly reduced the Cl(u) of endogenous catecholamines (by 72-90%) and of infused 3H-catecholamines (by 49-69%). Moreover, it preferentially inhibited the renal excretion of those components of urinary dopamine and noradrenaline which were derived from the kidney. Therefore, disprocynium24 inhibits the tubular secretion of catecholamines and, hence, organic cation transport in the kidney. This conclusion was substantiated by the observation that disprocynium24 did not alter the glomerular filtration rate.

Animals↗
PubMed1995

Effects of inorganic mercury (Hg2+) on calcium channel currents and catecholamine release from bovine chromaffin cells.

The effects of inorganic mercury (Hg2+) on calcium channel currents and the potassium-evoked catecholamine release of bovine chromaffin cells in culture were examined. The effects of cadmium (Cd2+), known to block calcium channels and reduce catecholamine release of chromaffin cells, were studied for comparison. Calcium channel currents were recorded in the whole-cell configuration of the patch-clamp technique. Hg2+ is a potent calcium channel blocker in bovine chromaffin cells. The IC50 value is about 3 microM, the Hill slope 1.46. In a concentration of 100 microM, Hg2+ blocked the currents completely; 100 microM Cd2+ had the same effect. Potassium-evoked catecholamine release from chromaffin cells was measured at different time-points with high-performance-liquid-chromatography (HPLC) under control conditions and in the presence of different Hg2+ concentrations. Low Hg2+ concentrations (0.1 and 1 microM) did not affect the amount of the catecholamines epinephrine (E) and norepinephrine (NE) which was released. Under identical conditions 1 microM Cd2+ also had no effect on release. With 10 microM Hg2+ there was a time-dependent increase in the potassium-evoked catecholamine release (by 27% after 8 min). The E/NE ratio was not altered, suggesting that the release of both hormones was increased similarly. In contrast to this, the release was slightly reduced with 10 microM Cd2+. In the presence of 100 microM Hg2+, there was a reduction of the release during an early phase, followed by an increase. The reduction is most probably due to the fast and effective calcium channel block by Hg2+ in this high concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

d-Amphetamine-induced hepatotoxicity: possible contribution of catecholamines and hyperthermia to the effect studied in isolated rat hepatocytes.

Amphetamines are indirect-acting sympathomimetic drugs widely abused due to their physical and psychostimulating effects. However, the use of these drugs has been associated with numerous reports of hepatotoxicity. While glutathione depletion induced by amphetamines contributes to the exposure of hepatocytes to oxidative damage, other indirect effects attributed to amphetamines may have a role in cell injury. To examine this possibility, Wistar rats were used for plasma measurements of d-amphetamine and catecholamines (noradrenaline, adrenaline and dopamine) (15 min) after i.p. injection of d-amphetamine (5, 20 and 80 mg/kg). Freshly isolated rat hepatocytes were put into contact for 2 h with concentrations of d-amphetamine and catecholamines similar to those found in vivo. Since hyperthermia is a common consequence of acute amphetamine intake, the study using isolated hepatocytes was conducted at 37 degrees C and also at 41 degrees C in order to simulate high temperature levels. We found that hyperthermia was an important cause of cell toxicity: in vitro, a rise in incubation temperature from 37 to 41 degrees C causes oxidative stress in freshly isolated rat hepatocytes, as shown by a depletion of reduced glutathione (GSH; 23%), an increase of oxidized glutathione (GSSG; 157%), the induction of lipid peroxidation with 77% increase of thiobarbituric acid substances TBARS) and the consequent loss of cell viability (< or = 44%). Single treatment of isolated hepatocytes with catecholamines at 37 degrees C induced lipid peroxidation (29% increase of TBARS) but had no effect on glutathione or cell viability. Conversely, a single treatment with d-amphetamine induced glutathione depletion (< or = 24% depletion of GSH) with no effect on lipid peroxidation or cell viability. Also, d-amphetamine potentiated the induction by catecholamines of lipid peroxidation at 37 degrees C (< or = 48% increase of TBARS), while concomitant treatment of d-amphetamine and catecholamines potentiated cell death at 41 degrees C (< or = 56% of cell death) although no effect on viability was seen at 37 degrees C. It is concluded that the aforementioned modifications induced by d-amphetamine in vivo are cytotoxic to freshly isolated rat hepatocytes.

Amphetamines↗
PubMed1998

An active metabolite of carbamazepine, carbamazepine-10,11-epoxide, inhibits ion channel-mediated catecholamine secretion in cultured bovine adrenal medullary cells.

We have recently reported inhibitory effects of carbamazepine (CBZ) on ion channel-mediated secretion of catecholamines in bovine adrenal medullary cells. Here, we report the effects of carbamazepine-10,11-epoxide (CBZ-E), an active metabolite of CBZ, and carbamazepine-10,11-diol (CBZ-D), a non-active metabolite, on 22Na+ influx, 45Ca2+ influx and catecholamine secretion in cultured adrenal medullary cells. CBZ-E, but not CBZ-D inhibited 22Na+ influx, 45Ca2+ influx and catecholamine secretion induced by carbachol or veratridine with a half-maximal inhibitory concentration (IC50) of 0.26 or 0.68 microg/ml, respectively. CBZ-E also inhibited high K+-evoked 45Ca2+ influx and catecholamine secretion (IC50 = 0.3 microg/ml), but CBZ-D did not. These findings suggest that CBZ-E, but not CBZ-D, attenuates catecholamine secretion by inhibiting nicotinic acetylcholine receptor-associated ion channels, voltage-dependent Na+ channels and voltage-dependent Ca2+ channels in the cells. This inhibition of CBZ-E as well as CBZ may be related to the clinical effects in neuropsychiatric disorders.

Adrenal Medulla↗