Concentrations Of Chlorpromazine Research Articles

Evidence that imidazol(id)ine- and sulphonylurea-based antagonists of cromakalim act at different sites in the rat thoracic aorta.

1. Ring segments of rat thoracic aorta were suspended in organ baths to record isometric tension. Tissues were precontracted with K+ (20 mmol/L), and full concentration-relaxation curves constructed to cromakalim (0.01-30 mumol/L) in the absence and presence of increasing concentrations of glibenclamide, glipizide, tolbutamide (the sulphonylureas), alinidine (an imidazolidine), phentolamine (an imidazoline), and chlorpromazine (the phenothiazine derivative). Whereas the active sulphonylureas, glibenclamide and glipizide, displayed classical competitive antagonism, the remaining compounds (alinidine, phentolamine and chlorpromazine) caused shifts in the cromakalim concentration-effect curves associated with a reduction in the slope and maximum response. 2. A single concentration of each antagonist was selected and the shift in the concentration-effect curve determined. The possibility that sulphonylurea and imidazol(id)ine antagonists act at different sites was tested using the concentration-ratio method for combined antagonists described by Paton and Rang (1965). The combination of alinidine and phentolamine (collectively called imidazol(id)ines) at a number of different concentrations (10-30 mumol/L) resulted in a concentration-ratio to cromakalim which was additive, suggesting a common site of action. Similar results were obtained when examining the interaction between two sulphonylurea compounds (glibenclamide and glipizide). However, the interaction between sulphonylurea (glibenclamide) and imidazol(id)ine (alinidine) produced concentration-ratios which were multiplicative, suggesting a different or additional site of action for compounds from these two groups. Results indicated that chlorpromazine was able to block cromakalim via an action at the same site where alinidine and phentolamine act.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes induced by chlorpromazine and heat in erythrocyte membranes

1. 1. Chlorpromazine which is generally known as a tranquilizer, can be used to elucidate the role of membrane modification on the erythrocyte thermal properties. 2. 2. In this paper we examined the lipid fluidity of erythrocyte membranes and membrane protein conformational changes in cells pretreated with chlorpromazine and subsequently subjected to heating. 3. 3. The presence of drug before heating modified the response of erythrocytes to heat. 4. 4. These data show that low concentration of chlorpromazine protected pig erythrocytes from thermal haemolysis. Moreover, chlorpromazine at this concentration caused a modification of membrnes leading to induction of alterations in protein conformation.

Chlorpromazine increases the turnover of metabolically active phosphoinositides and elevates the steady-state level of phosphatidylinositol-4-phosphate in human platelets

Non-permeabilizing concentrations (<40 μM) of chlorpromazine (CPZ) increase the radioactivity of phosphatidylinositol-4-phosphate (PIP) in platelets pre-labelled with [ 32P]P i, but the biochemical mechanisms underlying this increase are poorly understood. Incubation of [ 32P]P i-labelled, gelfiltered platelets with 25 μM CPZ for 10 min increased: (1) the mass of PIP from 315 to 476 nmol 10 11 platelets but not the total inositol phospholipid mass, (2) the specific phosphodiester radioactivities in phosphatidylinositol (PI), PIP and phosphatidylinositol-4,5-bisphosphate (PIP 2) by 34, 63 and 37%, respectively, and (3) the specific phosphomonoester radioactivities in PIP and PIP 2 by 53 and 10%, respectively. In control platelets (no CPZ) the specific radioactivity of the phosphodiester was the same in PI, PIP and PIP 2, and the specific radioactivity in the phosphomonoester in PIP and PIP 2 was 55% of that of the γ-phosphoryl in ATP, measured as metabolically active, actin-bound ADP. These results suggest that 55% of each of PI, PIP and PIP 2 constitutes a metabolic pool which is labelled by 32P in the platelets, while the remainder is in a metabolically inactive pool and not labelled. CPZ has two major effects: (1) CPZ interferes with the kinase and phosphohydrolase reactions that maintain the steady-state level of PIP in the metabolic phosphoinositide pool, resulting in a 92% increase in the PIP level of this pool, and (2) CPZ causes synthesis (45% in 10 min) of new phosphodiester in the metabolically active phosphoinositides by tentative stimulation of the turnover of the phosphoinositide cycle, de novo phosphoinositide synthesis and/or diacylglycerol formation through phospholipases C and D. The marked alteration by CPZ of phosphoinositide metabolism may be part of the mechanism by which this drug effects its psychotropic action.

Chlorpromazine induced aggregation of normal human hemoglobin. Electron microscopic evidence

Normal human hemoglobin exceeding a certain minimum concentration (called critical aggregation concentration) undergoes aggregation in presence of the psychotherapeutic drug chlorpromazine (CPZ). The critical aggregation concentration decreases with the increase of CPZ concentration. Electron micrographs of CPZ-treated hemoglobin clearly indicate that the aggregates of hemoglobin are in filamentous form of average width 75 ± 8 Å. A possible mechanism for such aggregation has been discussed.

Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei.

Almost all the polyamine-stimulated protein kinase activity associated with the chromatin fraction of nuclei purified from etiolated pea (Pisum sativum L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.35 molar NaCl. This protein kinase can be further purified over 2000-fold by salt fractionation and anion-exchange and casein-agarose column chromatography, after which it is more than 90% pure. The purified kinase has a specific activity of about 650 nanomoles per minute per milligram protein in the absence of polyamines, with either ATP or GTP as phosphoryl donor. Spermidine can stimulate its activity fourfold, with half-maximal activation at about 2 millimolar. Spermine and putrescine also stimulate activity, although somewhat less effectively. This kinase has a tetrameric alpha 2 beta 2 structure with a native molecular weight of 130,000, and subunit molecular weights of 36,000 for the catalytic subunit (alpha) and 29,000 for the regulatory subunit (beta). In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II. The pea kinase can use casein and phosvitin as artificial substrates, phosphorylating both the serine and threonine residues of casein. It has a pH optimum near 8.0, a Vmax of 1.5 micromoles per minute per milligram protein, and a Km for ATP of approximately 75 micromolar. Its activity can be almost completely inhibited by heparin at 5 micrograms per milliliter, but is relatively insensitive to concentrations of staurosporine, K252a, and chlorpromazine that strongly antagonize Ca(2+) -regulated protein kinases. These results are discussed in relation to recent findings that casein kinase 2-type kinases may phosphorylate trans-acting factors that bind to light-regulated promoters in plants.

A model for the cytotoxic effects of amphiphilic chemicals in marine organisms using 3T3-cells

3T3-cells have been used as an in-vitro model of a phagocytically active marine organism such as Mytilus edulis. 3T3-cells are very sensitive to low concentrations of chlorpromazine (which inhibited mitochondrial reduction of tetrazolium to formazan by 50%—the IC 50 value was 15 μm). The metabolites 6,9-dihydroxychlorpromazine and 7-hydroxychlorpromazine are equitoxic (IC 50 values were 15 and 20 μm, respectively), but 7-hydroxychlorpromazine sulphoxide and 3,8-dihydroxychlorpromazine are less toxic (IC 50 values in the range 100–1000 μm). These data suggest that oxidation of the 6,7,8 or 9 positions may be a key factor in chlorpromazine toxicity in 3T3-cells and raise the possibility of a role for reactive oxygen injury. This is supported by the observation that vitamin E and l-ascorbic acid significantly protect these cells from chlorpromazine toxicity.

Involvement of Ca 2+ in the regulation of hyphal extension and branching in Fusarium graminearumA 3/5

In Fusarium graminearum, low concentrations (30–80 n M) of the Ca 2+ ionophore A23187 increased mean hyphal extension rate ( E) and hyphal growth unit length ( G), and thus, treated mycelia became more sparsely branched. This response of F. graminearum to low concentrations of A23187 was antagonized by low concentrations (10 μ M) of trifluoperazine (a calmodulin antagonist). By contrast, concentrations of A23187 above ca. 0.1 μ M decreased E and G, and thus, treated mycelia became more highly branched. High concentrations (100–200 μ M) of trifluoperazine, W-7, and chlorpromazine (all calmodulin antagonists) also caused decreases in E and G, as did three organic (cinnarizine, nifedipine, and nicardipine) and one inorganic (cobalt chloride) Ca 2+ channel blockers. At the concentrations employed to induce changes in G and E, the above compounds had no effect on specific growth rate. These results suggest that Ca 2+ is involved in the regulation of hyphal extension and branching in fungi.

THE BIPHOTONIC PHOTOIONIZATION OF CHLORPROMAZINE DURING CONVENTIONAL FLASH PHOTOLYSIS: SPIN TRAPPING RESULTS WITH 5,5‐DIMETHYL‐1‐PYRROLINE‐N‐OXIDE

A novel combination of conventional flash photolysis and electron spin resonance (ESR) spin-trapping has been used to demonstrate that photoionization of chlorpromazine (CPZ), and the concomitant production of hydrated electron, occurs through a stepwise biphotonic mechanism during conventional flash photolysis at wavelengths above 290 nm. The production of hydrated electron in the flash photolysis experiment has been monitored and quantified through the use of the spin trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The effects of nitrous oxide, varying concentrations of CPZ and DMPO, and a range of flash intensities on the ESR spectra of the observed spin adducts of DMPO are discussed. The use of ESR spin trapping to monitor hydrated electron yields in flash photolysis experiments has the potential to permit the use of a much wider range of flash intensities than is typically possible with conventional optical experiments. Thus, there is a greater possibility of distinguishing between monophotonic and biphotonic processes.

Effect of Storage on the Plasma Concentration of Chlorpromazine and Six of Its Metabolites

The concentrations of chlorpromazine (CPZ) and six of its metabolites in patient plasma samples that had been stored for 24 h at -20 degrees C, for 1 week at -20 degrees C, and for 4 weeks at -70 degrees C were compared. The concentrations of CPZ and six of its metabolites in human plasma spiked with known concentrations and stored at -70 degrees C for either 3 or 12 months were also compared. No significant difference was seen in the concentrations after storage under nitrogen and analysis by a high-performance liquid chromatography technique.

Cholestasis and changes of portal pressure caused by chlorpromazine in the perfused rat liver

Chlorpromazine (10 μmol/L) causes a marked increase in portal pressure in perfused rat liver. Simultaneously, oxygen consumption, hepatic clearance of taurocholate and bile flow are diminished. These effects are prevented by the cyclooxygenase inhibitors indomethacin (15 μmol/L), acetylsalicylate (3 mmol/L) or ibuprofen (200 μmol/L). On addition of chlorpromazine the liver releases increased amounts of prostaglandin D2; this increase does not occur in the presence of indomethacin. At higher concentrations of chlorpromazine (100 μmol/L) the inhibition of taurocholate clearance and bile flow is accompanied by only a moderate increase of portal pressure, and indomethacin is without effect. At this high concentration, substantial cell damage, as indicated by the release of lactate dehydrogenase, is present. We conclude that arachidonic acid—derived metabolites, notably prostanoids, are involved in the inhibition of bile flow and of taurocholate clearance observed at low concentrations of chlorpromazine. The data suggest that changes in the microcirculation are responsible for the impairment of the liver functions. At higher concentrations of chlorpromazine the cell toxicity of the drug becomes prominent. (HEPATOLOGY 1991;13:216–221).

Cholestasis and changes of portal pressure caused by chlorpromazine in the perfused rat liver

Chlorpromazine (10 mumol/L) causes a marked increase in portal pressure in perfused rat liver. Simultaneously, oxygen consumption, hepatic clearance of taurocholate and bile flow are diminished. These effects are prevented by the cyclooxygenase inhibitors indomethacin (15 mumol/L), acetylsalicylate (3 mmol/L) or ibuprofen (200 mumol/L). On addition of chlorpromazine the liver releases increased amounts of prostaglandin D2; this increase does not occur in the presence of indomethacin. At higher concentrations of chlorpromazine (100 mumol/L) the inhibition of taurocholate clearance and bile flow is accompanied by only a moderate increase of portal pressure, and indomethacin is without effect. At this high concentration, substantial cell damage, as indicated by the release of lactate dehydrogenase, is present. We conclude that arachidonic acid-derived metabolites, notably prostanoids, are involved in the inhibition of bile flow and of taurocholate clearance observed at low concentrations of chlorpromazine. The data suggest that changes in the microcirculation are responsible for the impairment of the liver functions. At higher concentrations of chlorpromazine the cell toxicity of the drug becomes prominent.

Plasmodium falciparum: modulation by calcium antagonists of resistance to chloroquine, desethylchloroquine, quinine, and quinidine in vitro

Intrinsic interactions of calcium antagonists (broadly defined) and quinoline-containing antimalarial drugs were evaluated against chloroquine-sensitive and chloroquine-resistant clones of Plasmodium falciparum in vitro. Verapamil, D-600 (methoxyverapamil), Ro 11-2933/001 (tiapamil analogue), chlorpromazine, SKF 21133-A (chlorpromazine analogue), and diltiazem each potentiated the efficacy of the quinoline-containing antimalarials chloroquine, desethylchloroquine, and quinine with a chloroquineresistant clone of P. falciparum, but did not affect the response of the quinoline-susceptible clone. Similar concentrations of either chlorpromazine or Ro 11-2933/001 lowered the IC 50 of the resistant clone to approximately the same level as that observed for the sensitive clone for each of the quinolines tested. This reversal of resistance by many of the same calcium antagonists underscores the similarities in one mechanism of multi-drug resistance in neoplastic cells and quinoline-resistance in P. falciparum.

Bioequivalence of two Thorazine Tablet Formulations Using Radioimmunoassay and Gas Chromatographic-mass Spectrometric Methods

Two analytical methods for the analysis of chlorpromazine (CPZ), a radioimmunoassay (RIA) and a GLC-MS method, were compared in a bioequivalence study of two CPZ tablet formulations (Thorazine: film coated and sugar coated). Thirty-six nonsmoking, healthy, male volunteers completed the study. Each subject ingested single doses (2 × 25 mg) of the test (T) and the reference (R) formulations in a two-way crossover design with a two-week drug-free interval between doses. Following each administration, plasma concentrations of CPZ were monitored over a period of 24 h by both RIA and GLC-MS methods. Plasma concentrations and pharmacokinetic parameters determined by either analytical method showed wide intersubject variation, with the GLC-MS data showing relatively higher magnitude of intersubject variation than the RIA data. In general, plasma concentrations measured by RIA were significantly different from those measured by GLC-MS (paired t tests: p < 0.0001). As indicated by the regression analysis, concentrations determined by RIA were 1.3–1.4 times higher than those determined by GLC-MS. There were strong and significant correlations between the two methods for both T and R (r > 0.75: p < 0.0001). Similar statistical relationships were found between the plasma concentrations of CPZ determined by the two methods at each sampling time and the bioequivalence parameters area under the plasma level versus time curves up to the last measurable concentration (AUC0t) and the maximum plasma concentration (Cmax). Bioequivalence parameters AUC0t, AUC0∞, and (Cmax). determined separately from the data obtained by the two methods for the two formulations were examined by analyses of variance (ANOVA) and other criteria and tests for bioequivalence. Results of ANOVA, confidence intervals of test/reference ratios of AUC0t, AUC0∞, and Cmax, and statistical tests for bioequivalence indicated that, except for Cmax by GLC-MS, data generated by both methods indicated bioequivalence of the two formulations (i.e., test/reference ratio was within 100 ± 20%). The experiments suggest that despite significant differences between the absolute plasma concentration values obtained, both methods yielded data for the two formulations which demonstrated that they were bioequivalent.

Accumulation of inositol phosphates induced by chlorpromazine in C6 glioma cells.

Chlorpromazine, a cationic amphiphilic drug known to affect phospholipid metabolism, greatly increases the generation of inositol phosphates in C6 glioma cells. When a pulse-chase protocol with myo-[2-3H]inositol as the radioactive precursor was used, the peak increase in radioactivity of inositol phosphates was observed at 20 min. The drug decreased inositol tetrakisphosphate labeling as a percentage of inositol trisphosphate in a dose-dependent manner. It also increased the labeling of the inositol-containing phospholipids, the precursors of the inositol phosphates. The increase in radioactivity of both phospholipids and inositol phosphates was dose-dependent, but appeared also to be a function of the time of exposure of the cultures to the drug, suggesting that the concentration of chlorpromazine in the cell, and not that in the medium, is the critical factor. The optimum concentration for maximum phospholipid labeling was lower than that eliciting maximum generation of inositol phosphates. The data suggest that the mechanism probably does not involve cell-surface receptors, but rather may consist of a direct effect of chlorpromazine on phosphoinositidase C and possibly other enzymatic reactions concerned with the metabolism of inositol phosphates.

Tegumental Ca-stimulated adenosine triphosphatase activity in adult Schistosoma mansoni worms

A Ca-stimulated ATPase activity (pH 9.5) associated with the tegumental membrane enriched (TME) fraction of Schistosoma mansoni adults was partially inhibited by NAP-taurine or by increasing concentrations of chlorpromazine; endogenous calmodulin was found associated with the TME fraction. A similar activity (pH 8.6) was histochemically visualized within the tegument of fixed worms on the cytoplasmic leaflet of both the double surface membrane and the basement membrane; this reaction was inhibited by 1 microM chlorpromazine and it was also observed on the inner side of double membrane vesicles present in the TME fraction. No ATPase activity could be seen at alkaline pH with added Mg or Na/K ions. Without ATP, the addition of external Ca to the fixed worms induced the appearance of lead precipitates on the tegumental discoid bodies; this reaction was inhibited by molybdate and not by chlorpromazine. The intrategumentary regulation of calcium by the systems described and the possible use of phenothiazines against schistosomes are discussed.

Effects of chlorpromazine and trifluoperazine on choline metabolism and phosphatidylcholine biosynthesis in cultured chick heart cells under normoxic and anoxic conditions

The effects of chlorpromazine and trifluoperazine on phosphatidylcholine biosynthesis in the heart were investigated in isolated cardiac cells under normoxic and anoxic conditions. The cells were obtained from 7-day-old chick embryos and were maintained in culture. After 96 hr, cells were maintained either in an incubator with oxygen at room air concentration (normoxia) or in an incubator containing 95% nitrogen and 5% CO 2 (anoxia). Pulse chase experiments with [ methyl- 3H]choline were conducted using a 2-hr incubation with choline. Chlorpromazine and trifluoperazine at 10 −5M produced a significant ( P < 0.05) increase in the incorporation of choline into both phosphocholine and phospholipid. High concentrations of chlorpromazine or trifluoperazine i.e. 10 −4M, damaged myocardial cells as reflected in a significant ( P < 0.05) reduction in cellular protein and a further reduction in labelled choline in phosphocholine or phospholipid after adjusting for the lower protein concentrations. Anoxia altered choline metabolism but 6 hr of anoxia was the minimum time needed for the effect to be observable. Anoxia, for 24 hr, produced a significant ( P < 0.05) reduction in labelled choline in phosphocholine without a significant change in incorporation of label in phospholipid or cellular protein. Both chlorpromazine and trifluoperazine at 10 −5M prevented anoxic-induced changes in phosphocholine metabolism. Thus, chloropromazine and trifluoperazine affect phospholipid biosynthesis in cardiac cells and prevent anoxia-induced changes in phosphatidylcholine biosynthesis.

Chlorpromazine, administered in vivo and in vitro, inhibits the efflux of bile acids in freshly isolated rat hepatocytes.

Although it has been speculated that chlorpromazine may alter the transhepatic movement of bile acids from plasma to bile, the effect of chlorpromazine on various determinants of bile acid transport in isolated rat hepatocytes remains incompletely defined. In particular, there is little information about the effect of chlorpromazine on the release of bile acids from freshly isolated hepatocytes. Therefore, we examined the effect of chlorpromazine, administered in vivo and in vitro, on the efflux rate of radiolabeled bile acids in freshly isolated rat hepatocytes. In an isolated haptocyte system, it is not possible to distinguish the sinusoidal plasma membrane function of efflux (back diffusion) from the canalicular plasma membrane function of excretion. Therefore, efflux, as used in this manuscript, reflects both back diffusion and excretion. In vitro, chlorpromazine produced a rapid dose dependent significant (P less than 0.05) decrease of the bile acid efflux rate in freshly isolated hepatocytes. This decrease in bile acid efflux was observed at chlorpromazine concentrations which did not alter hepatocyte plasma membrane permeability (viability), as measured by intracellular potassium content, release of lactate dehydrogenase, and trypan blue exclusion. Moreover, in freshly isolated hepatocytes from chlorpromazine pretreated rats, a significant (P less than 0.05) decrease in the bile acid efflux rate was also observed, and this decrease in efflux was similar in magnitude to the decrease in bile acid efflux observed following exposure of freshly isolated hepatocytes to chlorpromazine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Dependence of Somatostatin (SRIF) Release and Cyclic AMP Levels in Cultured Diencephalic Neurons

Calmodulin has been reported to be involved in the Ca2+-dependent hypothalamus in vitro. The present experiments were undertaken to determine whether at an early stage of development (in diencephalic primary cultures secreting SRIF, on the 11th day) the activation of a Ca2+-calmodulin kinase system is also involved in the release of the peptide. Since a calmodulin-dependent adenylate cyclase activity has been detected in the brain, we measured intracellular cyclic AMP accumulation as an additional parameter of calmodulin activity. SRIF release and cyclic AMP accumulation were stimulated by K+ (56 mM) and by the Ca2+ ionophores ionomycin (0.5 microM) and A 23187 (in a dose-dependent manner). Incubation of cells in Ca2+-free Locke medium or in the presence of Co2+ (1 mM) completely blocked ionophore-induced SRIF release and cyclic AMP accumulation. Three calmodulin antagonists (calmidazolium, W-7, and chlorpromazine) and two blockers of calmodulin-dependent kinase (phenytoin and diazepam) were tested on evoked-SRIF release and cyclic AMP formation. Neither W-7 nor calmidazolium modified A 23187-induced SRIF release at any dose tested, although they inhibited, in a dose-dependent manner, the stimulatory effect of the Ca2+ ionophore on cyclic AMP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

The kinetics of drug–membrane interactions in human erythrocytes from neonates

The kinetics of drug-membrane interactions of erythrocytes from neonates were compared with those from adults by monitoring the time course of the shape transformations and vesicle release caused by drugs, using a light microscope--video recording technique. Both crenation caused by lysophosphatidylcholine (LPC) and cupping caused by chlorpromazine (CPZ) took place more slowly in the neonatal cells than in the cells from adults. The equilibrium concentrations of LPC and CPZ in erythrocytes did not differ significantly between the neonates and adults, however. The slower responses of the neonatal erythrocytes can be explained by the presence of negatively charged phosphatidylethanolamine and phosphatidylserine in the outer layer of the erythrocyte membrane, which may reduce the rate of incorporation of amphipathic LPC and attract cationic CPZ to remain in the outer membrane layer, lowering the rate of inward bending of the membrane normally caused by CPZ.

Influence of chlorpromazine on the transverse mobility of phospholipids in the human erythrocyte membrane; relation to shape changes

The influence of chlorpromazine (CPZ) on the transverse mobility of spin-labeled phospholipids incorporated into human erythrocytes was investigated by electron spin resonance. The very slow transverse diffusion of phosphatidylcholine, as well as the absence of transverse mobility of sphingomyelin were not modified even by sublytic concentrations ( ≈ 1 mM ) of CPZ. On the other hand, the rapid outside-inside translocation of the aminophospholipids (Seigneuret and Devaux (1984) Proc. Natl. Acad. Sci. USA 81, 3751–3755), was slightly hindered in CPZ containing membranes. If the spin-labeled aminolipids were incorporated in erythrocytes and allowed to flip to the inner monolayer before CPZ addition, a fraction of the spin labels (10–15%) flipped back instantaneously from the inner to the outer leaflet, upon incubation with CPZ. Similar experiments carried out with spin-labeled phosphatidylcholine and spin-labeled sphingomyelin showed that a fraction of the spin-labeled choline derivatives flip instantaneously to the inner leaflet if CPZ was added after the spin labels. Addition of lysophosphatidylcholine had no effect on the spin-labeled phospholipid redistribution nor on their transmembrane mobility. We interpret the immediate effect of CPZ addition as being due to a reorganization of the bilayer accompanying the rapid CPZ membrane penetration, phenomenon which is independent of the CPZ effect on the steady-state activity of the ‘aminophospholipid translocase’, the latter effect being probably a direct CPZ-protein interaction. By comparison of the time course of phosphatidylserine transverse diffusion in control discocyte cells and in CPZ-induced stomatocytes, we infer that the difference in cell shape is not a major factor in the regulation of the active inward transport of aminophospholipids in human erythrocytes.