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PubMed1977

Effect of maternal malnutrition on matrix cell proliferation in the cerebrum of mouse embryo: an autoradiographic study.

Thirty pregnant mice were undernourished by providing low protein diets (PM) or providing approximately one-third their normal diets (PCM) for 9 days from the 8th to the 16th day of gestation. Another 15 pregnant mice, which were fed a normal diet, served as the control. On the 16th day of gestation, all animals were injected with a single does of [3H]thymidine and were killed one by one at 1- or 2-hr intervals. Mean litter size was statistically insignificant between the control group and two malnourished groups. There was, however, a significant difference in mean body weight between the control group and two malnourished groups (P less than 0.005). The cerebral cortex at this stage of development consisted of three different layers, i.e., the cortical plate, the migratory zone, and the matrix layer. The width of the cortical plate of the malnourished embryos was significantly smaller (P less than 0.001). There was, however, no significant difference in width of the migratory zone between the control and the malnourished groups. The width of the matrix layer in PM was significantly smaller (P less than 0.001), but that of PCM showed no significant difference from the control (P greater than 0.1). Coronal section of the brains of the embryos were processed for autoradiography. Labeled cells were found almost exclusively at the matrix layer surrounding the lateral ventricels. Labeling index counted in the matrix layer after 1 or 2 hr of [3H]thymidine injection indicated that more than 30% of the cells in this layer were always synthesizing DNA in each group of embryos. The generation times of the matrix cell, precursor of the neurons, in the matrix layer were approximately 18.5 hr in the control and 21.5 hr and 21.8 hr in the malnourished embryos, thus indicating about 3 hr of prolongation in the latter. DNA synthetic time was about 6.5 hr in the control and 7.0 hr and 7.0 hr in the two malnourished groups. The postduplication time was about 2.5 hr in the control and 3.0 hr and 3.5 hr in the malnourished. The preduplication time was about 8.8 hr in the control and 10.6 hr and 10.3 hr in the malnourished.

Animals↗

PubMed1988

The effects of cortisol, vasopressin (AVP), and corticotropin-releasing factor administration on pulsatile adrenocorticotropin, alpha-melanocyte-stimulating hormone, and AVP secretion in the pituitary venous effluent of the horse.

Plasma ACTH, arginine vasopressin (AVP), and alpha MSH were measured in pituitary venous effluent at 5-min intervals from five unanesthetized horses during cortisol infusion and after an iv bolus of AVP or ovine (o) CRF. In control experiments (no hormone) there was a significant overall correlation between the timing of concentration changes in ACTH and alpha MSH. Cortisol infusion increased jugular cortisol levels by 70% and was associated with a reduction in mean ACTH, AVP, and alpha MSH secretion rates and ACTH peak secretion rate, but did not alter the observed pulse frequencies of these hormones. Administration of AVP raised plasma concentrations to a level comparable to the spontaneous peaks in pituitary venous blood and resulted in an increase in the secretion of ACTH and alpha MSH in all horses. Furthermore, spontaneous AVP peaks occurred in pituitary venous blood between 90 and 180 min after AVP injection, indicating that the exogenous hormone did not suppress AVP secretion. oCRF administration led to a prolonged elevation in plasma CRF and an increase in secretion of ACTH and alpha MSH, but not AVP, in all horses. The pulsatile secretion of ACTH and alpha MSH was maintained despite plasma CRF levels in excess of 400 pmol/liter, and the timing of concentration changes in AVP and ACTH continued to be highly correlated. It is concluded that pulsatile ACTH secretion continues during cortisol, oCRF, or AVP administration. Like that of ACTH, alpha MSH secretion is stimulated by oCRF and AVP administration and suppressed by cortisol. Although the timing of concentration changes in ACTH and alpha MSH is highly correlated, the correlation of the actual concentrations of these two hormones varies considerably in different animals.

Adrenocorticotropic Hormone↗

PubMed1978

Prolonged negative feedback suppression after estradiol administration: proposed mechanism of eugonadal secondary amenorrhea.

The finding of normal gonadotropin and estradiol levels in eugonadal women with secondary amenorrhea suggests a disordered feedback relationship of the hypothalamic-pituitary-ovarian axis. To identify possible defects in negative and positive feedback, we compared the effects of five daily injections of 17 beta-estradiol (E2) in 13 normal women and 11 eugonadal patients with absent cyclic menses. The suppression phase of negative feedback was normal, as LH and FSH were similarly lowered in both groups on day 3. Continued LH (P less than 0.01) and FSH (P less than 0.02) inhibition on day 10 of the protocol, 5 days after the last E2 injection, indicated a defect in the recovery phase of negative feedback in the 11 amenorrheic women. In the 4 patients studied gonadotropin suppression persisted for 3 weeks, E2 did not blunt pituitary responsiveness to GnRH in the amenorrheic women, suggesting a central nervous system site for prolonged gonadotropin inhibition. Nine normal but only 2 amenorrheic women X2 = 4.15; P less than 0.05) exhibited a positive feedback increase in LH on days 4-6. We propose that a defect in the recovery phase of negative feedback to E2 rather than absent positive feedback may be the dominant physiological abnormality which causes secondary amenorrhea by preventing early follicular phase gonadotropin increments and follicular maturation.

Adult↗

PubMed1990

Specific induction of fibronectin gene in rat liver by thyroid hormone.

The regulation of fibronectin (FN) gene expression by thyroid hormone was studied. Rats were rendered hypothyroid by thyroidectomy, and the administration of T4 or T3 was used to produce rats in various thyroid states. RNA was extracted from fresh liver, kidney, and heart, and FN mRNA was determined by dot blot hybridization with a 32P-labeled rat FN cDNA probe. The specificity of the hybridization was assessed by Northern blot analysis. In liver, thyroidectomy decreased the abundance of FN mRNA by half, and daily administration of physiological doses of T4 or T3 for 5-6 days restored FN mRNA to the control level. The administration of pharmacological doses of thyroid hormones induced a further increase in the abundance of FN mRNA. A significant dose-dependent correlation between serum levels of T4 and the abundance of FN mRNA was observed in liver. A receptor-saturating dose of T3 (200 micrograms) given to thyroidectomized rats produced a significant increase in FN mRNA within 6 h after injection, indicating that expression of the FN gene was induced relatively rapidly. Moreover, a nuclear run-off assay revealed that thyroid hormone induces expression of the FN gene at least in part at a transcriptional level. The amount of FN mRNA was also determined in kidney and heart of the same rats. Although the abundance of FN mRNA changed by thyroidectomy or the administration of thyroid hormone in those organs, the magnitude of changes were slight compared with those observed in liver. These results suggested that a marked and dose-dependent induction of the FN gene by thyroid hormone occurs specifically in liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Effects of diethyldithiocarbamate, a metabolite of disulfiram, on the pharmacokinetics of alcohol and acetaldehyde in the rat.

The effects of diethyldithiocarbamate (DDC), a metabolite of disulfiram which is known as Antabuse, on the blood concentrations of alcohol and acetaldehyde were determined simultaneously by head space gas chromatography in rats. After an intravenous injection of alcohol, the blood concentration of acetaldehyde was much lower than that of the alcohol. A pharmacokinetic model featuring the liver compartment for acetaldehyde was used to estimate pharmacokinetic parameters on the assumption that the distribution volumes of the central compartments were same for alcohol and acetaldehyde, and that the elimination rate of acetaldehyde from liver was large enough to isolate the liver compartment from the central compartment. The results showed that the clearance of alcohol was 0.0226 l/min/kg and the elimination rate constant of acetaldehyde from the liver compartment was very large and 35 min-1. The administration of DDC decreased the above significantly to 0.0132 l/min/kg and 20 min-1, respectively. After intravenous infusion of acetaldehyde, the time course of the blood concentration of acetaldehyde was analyzed by the one compartment model. The estimated elimination rate constants from blood and the distribution volume were in good agreement with those calculated from alcohol injection, indicating the appropriateness of the method used in this study. DDC had no effect on the elimination of infused acetaldehyde from blood indicating that the elimination may be due to the loss from lungs into breath, from skin surfaces and/or from the kidney but not by metabolism in the liver.

Acetaldehyde↗

PubMed1987

[Centrally and peripherally induced anorectic actions of salmon calcitonin (sCT) in rats: separation of its novel derivative [Gly8]-sCT].

It has been reported based on animal studies that salmon calcitonin (sCT), besides hypocalcemic action, exhibits a variety of pharmacological actions. The anorectic action has been observed to ensue not only by central administration but also by peripheral injection, indicating that in clinical use to induce hypocalcemia or for other therapeutic purposes, the anorectic action may develop as a side effect. While studying the anorectic effect of [Gly8]-sCT in rats, a derivative of sCT having rather stronger hypocalcemic potency than the mother molecule, it was found that on peripheral injection, the derivative practically lacks the anorectic effect. Thus, a pharmacological evaluation of the novel peptide was made. When injected subcutaneously in rats at a dose level of 1 U/kg, sCT and the derivative induced similar patterns of hypocalcemia in either of which hypocalcemia reached a peak between 1 and 3 hr after injection. No notable difference existed between the action of the two peptides. In rats which were trained to take the daily food need within 2 hr (17:00 approximately 19:00), an intracerebroventricular injection of 1 U/rat of either peptide 30 min before food presentation significantly reduced both food and water intake, causing a loss of body weight as compared with the control which received the injection of saline alone. By subcutaneous injection of 100 U/kg, sCT was also active to decrease food and water intake. The effect was found to last longer than 24 hr and to cause a marked loss in body weight. In contrast, such effects did not develop in rats treated with the derivative. Both peptides were able to suppress the specific binding of 125I-sCT to the membrane fraction of rat brain and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Key role of complement activation and platelet-activating factor in exudate formation in zymosan-induced rat pleurisy.

Involvement of complement and platelet-activating factor (PAF) in zymosan-induced rat pleurisy was examined. Only a very low level of complement remained in the exudate at 1-5 hr after zymosan injection, indicating that complement activation had occurred during this period in the pleural cavity. When rats were injected with cobra venom factor (CVF) 24 hr prior to the zymosan injection to deplete complement, the exudate volumes at 0.5 and 5 hr after zymosan injection were significantly reduced. Furthermore, combined treatment with CVF and CV-6209, an antagonist of PAF, also significantly suppressed the exudation but to no further extent than the suppression by CVF alone, suggesting that the level of complement depletion achieved was sufficient to halt PAF synthesis/release. To see if complement activation is involved in PAF production, we examined the PAF production by resident leukocytes in response to zymosan in vitro. When pleural leukocytes were stimulated with zymosan in the presence of rat serum, PAF-like activity both in the medium and in the cellular fraction increased. If the serum was heat inactivated, no PAF-like activity was detected. These results suggest that initial activation of the complement system may occur in the pleural cavity by zymosan and that the activated complement may then stimulate the production of PAF, which in turn elicits the exudate.

Animals↗

PubMed1979

High thyroid radiation dose associated with 131-I-19-iodocholesterol adrenal scanning.

We have examined two patients undergoing 131I-19-iodocholesterol adrenal scans in order to assess thyroidal radiation dose. Thyroid uptakes of 3--5% of the administered 2 mCi dose were found despite prior administration of Lugol's iodine. Analysis of serum samples over a ten day period after iodocholesterol injection indicated that less than 10% of the radioactivity was free iodide. Kinetic results showed a high value for the thyroid/plasma 131I ratio indicating thyroid retention of 131I. This was substantiated by thyroid scintigrams. The thyroid radiation dose was estimated to be 200--250 rad for the two patients. The associated carcinogenic risk is of sufficient magnitude, in our opinion, to warrant regular follow-up of all patients who have undergone 131I-19-iodocholesterol adrenal scanning.

19-Iodocholesterol↗

PubMed1990

Bioavailability of iron and cyanide from 59Fe- and 14C-labelled hexacyanoferrates(II) in rats.

"Soluble" (KFe(III)[Fe(II)(CN)6]) and "insoluble Prussian blue" (Fe(III)4[Fe(II)(CN)6]3 labelled with 59Fe either in the ferric (Fe(III)) or ferro (Fe(II)) position and 14C in the cyanide group were synthesized and administered intraperitoneally or orally to adult female rats with normal body iron stores. Following i.p. injection of KFe[Fe(CN)6], the colloidal complex is disintegrated into ferric iron and hexacyanoferrate(II) anion almost completely. About 96% of the ferric iron was retained in the body. Nearly 90% of both ferrous iron and cyanide were excreted with the urine within 7 days after i.p. injection, indicating that most of the undissociated hexacyanoferrate(II) anion ([Fe(CN)6]4-) was excreted through the kidney. Only 9% of the ferrous iron from [Fe(CN)6]4- was found mainly in carcass, liver and gut. As the 59Fe/14C-ratios in organs were found close to 1.0, the dissociation of the hexacyanoferrate(II) anion can only be small in vivo. No detectable 14CO2-activity (less than 0.01%) was monitored in the breath of rats after i.p. injection of the 14C-labelled KFe[Fe(CN)6], also indicating that no significant amounts of cyanide were released after parenteral administration. After oral administration of the soluble and insoluble Prussian blue, 0.3-0.7% of the ferric iron was absorbed and retained mainly in carcass, liver and blood. Only 0.06-0.18% of the ferrous iron was absorbed and mostly excreted with the urine (0.05-0.15%), so that only 0.01-0.03% of the oral ferrous 59Fe was retained in the body after 7-10 days. Very small fractions of 14C-label from the 14CN-group of the soluble and insoluble hexacyanoferrate(II) were observed in the exhaled air (0.04-0.08% of the oral dose). From the 14CO2-exhalation, the 14C-urine excretion and the distribution of iron in blood and organs it can be concluded that the hexacyanoferrate(II) moiety disintegrated only to a small extent in the intestinal tract after oral administration. From a dose of 36 mg hexacyanoferrate(II)/kg, an amount of free (non-complex bound) cyanide can be calculated which is in maximum two orders of magnitude below the LD100-level. Thus, the very low bioavailability of iron and cyanide from hexacyanoferrate(II) compounds after oral application is demonstrated in rats. In the case of a severe nuclear accident, appropriate doses of "soluble" and "insoluble" Prussian blue can be used as safe and effective antidote against radiocaesium contamination.

Animals↗

PubMed1988

A review of the animal pharmacology of roxatidine acetate.

Roxatidine acetate (TZU 0460/HOE 760) [N-(3-[3-(1-piperidinylmethyl)-phenoxy]-propyl)acetoxyacetamide hydrochloride] is a specific and competitive H2-receptor antagonist with a chemical structure different from those of cimetidine, ranitidine and famotidine. Roxatidine acetate and its main metabolite roxatidine inhibit histamine-induced gastric acid secretion in vitro with a potency greater than that of cimetidine, and in the range of that produced by ranitidine. Gastric acid secretion following stimulation with dibutyryl cyclic adenosine monophosphate remains unaffected by roxatidine acetate. In vivo experiments in rats and dogs confirm these in vitro findings. Thus, in rats roxatidine acetate inhibits gastric acid secretion with similar values following intraduodenal or intraperitoneal injection, indicating excellent absorption of the drug from the gastrointestinal tract. In all studies it was shown that roxatidine acetate was more potent than cimetidine. In rats single or repeated dosing with roxatidine acetate did not influence drug metabolising enzymes in the liver nor did the drug show antiandrogenic activity in long term animal studies. Extensive general pharmacological studies with roxatidine acetate demonstrate the lack of effects on the central nervous system, on gastrointestinal motility, the autonomic nervous system and the cardiovascular and urogenital systems. Studies on the pharmacokinetics and metabolism of roxatidine acetate demonstrate that there is a presystemic deacetylation producing the main metabolite roxatidine, which is responsible for the in vivo effects of the drug.

Animals↗

PubMed1979

The efficacy of intra-articularly administered MYC 2095, triamcinolone hexacetonide and placebo in gonarthritis. A combined double-blind clinical trial.

We report the results of a double-blind three-centre study, employing a cross-over design, set up to compare the efficacy of intra-articular injections of Myc 2095 (20 mg), triamcinolone hexacetonide (Lederspan) (20 mg) and placebo in 40 patients with synovitis of the knee joint. Each patient included in the study contributed data on 2 of the 3 treatment variables being compared. Seven clinical parameters were assessed every 6 weeks, while the doctor's and the patient's assessments were scored. Intra articular treatment both with Myc 2095 and triamcinolone hexacetonide proved to be effective. Placebo response was also very high. After the first Myc 2095 injection, improvement in "tenderness", "pain under load" and "swelling and hydrops" was significantly superior to that following placebo treatment. The evaluation of the second injections indicated a marked carry-over effect from the first course. This was also evident from the doctor's and patient's assessments. The importance of including a placebo in the evaluation of anti-phlogistic drugs in clinical trials, emerged from this study.

Adult↗

PubMed1975

Thyroid metabolism in the recessive sex-linked dwarf female chicken. 3. The influence of exogenous thyroid hormones in glycogen metabolism.

The influence of exogenous thyroid hormones on glycogen-body and liver glycogen was studied in fasted and full-fed 3 wk. old dwarf and non-dwarf White Leghorn chickens. The results indicated that in contrast to normals, the glycogen-body of the dwarf was still physiologically active at age 3 wks. and they also exhibited a relatively higher liver glycogen concentration. The liver glycogen concentration was significantly higher in T3-treated, full-fed dwarf chickens when compared with other groups. The data were interpreted to suggest that the differential response observed in both dwarf and non-dwarf chickens of increasing liver glycogen levels with T3 and T4 injections indicated that the proper ratios of serum T3:T4 were probably more vital to the normal metabolic functions than changes in the individual concentrations of either T3 or T4.

Animals↗

PubMed1975

Relief of pain following upper abdominal operations by thoracic epidural block with etidocaine.

Bupivacaine and etidocaine were compared in 0.375% and 0.5% solutions (without adrenaline) in a double-blind study in thoracic epidural analgesia following upper abdominal surgery. Special regard was taken to duration and adequacy of analgesia and changes in motor function. Duration of analgesia was roughly comparable for all four solutions. Bupivacaine 0.375% and etidocaine 0.5% seemed to be appropriate concentrations for adequate pain relief. Motor function, as assessed by changes in FVC, FEV1 and PEFR was not influenced to any greater extent. A progressive fall in FVC with successive injections, indicating increasing motor weakness, did not occur.

Abdomen↗

PubMed1975

Lysosomal degradation of cell organelles. II. Ultrastructural analysis of uptake and digestion of intravenously injected microsomes and ribosomes by Kupffer cells.

Rough and smooth microsomes, "mixed" or total microsomes, and ribosomes were isolated from one single rat liver and subsequently injected intravenously into a series of inbred rats. The uptake and the degradation of the injected organelles by Kupffer cells were followed by means of electron microscopic analysis. By 1 minute after injection, microsomes were seen attached to the surface of Kupffer cells separated by a gap of 200 to 300 A. No attachment to hepatocytes, fat-storing cells, or endothelial cells was seen. By 5 and 10 minutes, most microsomes were phagocytosed and sequestered in large numbers within single membrane-enclosed vacuoles or phagosomes. The engulfment proceeded by two mechanisms: (1) most frequently, flaplike processes of cytoplasm embraced aggregates of microsomes, concomitant with the formation of indention of the cytoplasm; (2) occasionally, single microsomal profiles were taken up by bristle-coated endocytic vacuoles. Ribosomes were also seen penetrating into the wormlike structures (micropinocytosis vermiformis) at the cell surface. At 30 minutes after injection, clear signs of alteration were noted starting with vesicle aggregation, clumping, and elongation of the microsomal profiles. The ribosomes were quickly stripped from their microsomal membranes and marginated to the inside of the vacuoles but separated from the limiting membrane by a distance of 200 to 300 A. By 1 and 2 hours, disruption of the vesicles into membrane fragments and formation of dense material in and between the profiles occurred. By 8 hours it was difficult to recognize the degradation products as membrane derivatives. The digestive vacuoles retained their size at this time interval. Typical pentalaminar structures were observed. By 14 to 24 hours the digestive vacuoles became electron lucent and appeared to shrink, and in addition to containing various types of granular material, many were laden with lipid-like droplets presumed to be conglomerates of phospholipid remnants. Rough microsomes, when compared to smooth microsomes, gave rise to more granular material within the digestive vacuoles. Ribosomes were still identifiable 24 hours after injection, indicative of a somewhat slower rate of degradation. Accumulation of various types of lipid-like droplets in the "residual bodies" was typical after microsomal injections. It is concluded that although microsomes appear to be phagocytosed at a quicker rate than mitochondria, they are digested within the lysosomal apparatus of the Kupffer cells at a somewhat slower rate. This especially seems to be the case for ribosomes. Heterophagy of microsomes is one source of residual bodies.

Animals↗

PubMed1975

The matrix of the optic vesicle-presumptive lens interface during induction of the lens in the chicken embryo.

The cell coats of the presumptive lens cells and the extracellular interface between the lens rudiment and optic vesicle were investigated in the chicken embryo throughout the period during which lens induction is presumed to take place. Histochemical methods showed that the cell coats contained both glycoproteins and glycosaminoglycans. Autoradiography after [3H]glucosamine injection indicated incorporation of the precursor with subsequent localization primarily at the cell surface. No obvious changes in the properties of the coat were noted with the progression of early lens morphogenesis. The extracellular matrix at the interface between ectoderm and optic vesicle also contained glycoprotein and glycosaminoglycan. There was a heavy concentration of [3H]glucosamine-containing macromolecules in the area. Electron microscopy revealed that the interface consisted of the basement membrane systems of lens and optic vesicle, fused with their external fibrillar layers. In contrast to the findings on cell coats the density of the interfacial matrix increases appreciably during the lens induction period. Evidence suggests that the cells of the two ocular epithelia are themselves the source of the matrix materials. It is proposed that the macromolecules excreted by the epithelial cells into the interface interact at different concentrations to form aggregates of various structure by a process of self-assembly. This may be reflected in the different ultrastructure of the layers of the interfacial matrix. Quantitative changes in the density of the matrix, leading to increased adhesion between lens rudiment and optic vesicle, may restrict the lateral spreading of the lens cells and so fix the basal area of the lens rudiment. This, together with continued cell replication, may produce the cell crowding, placode formation and invagination characteristic of lens morphogenesis.

Amylases↗

PubMed1975

Plasma levels following administration of sodium meclofenamate by various routes.

Sodium meclofenamate, an anti-inflammatory and anti-anaphylactic agent, was administered to cattle intravenously, orally and by intraruminal injection. Plasma levels of the free drug were estimated fluorimetrically at intervals after administration by each route. Levels fell rapidly, particularly during the first hour after intravenous injection. Differences between those plasma levels resulting from oral administration and those following intraruminal injection indicated that direct passage into the abomasum was achieved by the former method. Simultaneous intravenous and intrauminal injections achieved immediate high plasma levels and maintained levels adequate for efficacy for 24 h.

Administration, Oral↗

PubMedDate not supplied

Evaluation of alkylated derivatives of 99mTc-propylene amine oxime (99mTc-PnAO).

Several lipophilic di-alkylated derivatives of propylene amine oxime (PnAO were complexed to 99mTc. Assessment of the 99mTc-PnAO derivatives included biodistribution and qualitative autoradiography. All of the derivatives studied penetrated the intact blood-brain-barrier, with the 99mTc-dibutyl-PnAO complex exhibiting the lowest initial brain uptake while the 99mTc-diethyl-PnAO and the 99mTc-dipropyl-PnAO complexes possessing nearly identical initial brain uptake as compared to 99mTcPnAO. Qualitative autoradiographs revealed significant loss of image resolution with extended time post injection indicative of rapid radiopharmaceutical washout. Although increasing alkyl chain length did not enhance initial brain uptake, the data demonstrates that limited modification of the PnAO ligand structure can be performed without decreasing cerebral uptake of the respective 99mTc complex.

Animals↗

PubMed1992

Individual molecular species of phosphatidylcholine and phosphatidylethanolamine in myelin turn over at different rates.

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of the myelin membrane exhibit heterogeneity with respect to metabolic turnover rate (Miller, S. L., Benjamins, J. A., and Morell, P. (1977) J. Biol. Chem. 252, 4025-4037). To test the hypothesis that this is due to differential turnover of individual molecular species (which differ in acyl chain composition), we have examined the relative turnover of individual molecular species of myelin PC and PE. Phospholipids were labeled by injection of [2-3H]glycerol into the brains of young rats. Myelin was isolated at 1, 15, and 30 days post-injection, lipids were extracted, and phospholipid classes were separated by thin-layer chromatography. The PC and PE fractions were hydrolyzed with phospholipase C, and the resulting diacylglycerols were dinitrobenzoylated and fractionated by reverse-phase high performance liquid chromatography. The distribution of radioactivity among individual molecular species was determined. The labeled molecular species of myelin PC were 16:0-16:0, 16:0-18:0, 16:0-18:1, and 18:0-18:1, with most of the label present in 16:0-18:1 and 18:0-18:1. Changes in distribution of label with time after injection indicated that 16:0-18:1 turned over more rapidly than 18:0-18:1. The labeled molecular species of myelin PE were 18:0-20:4, 18:1-18:1, 16:0-18:1, 18:0-18:2, and 18:0-18:1. As with myelin PC, 16:0-18:1 (and 18:1-18:1) turned over more rapidly than 18:0-18:1. The relative turnover of individual molecular species of PC in the microsomal fraction from forebrain was also examined. The molecular species profile was different from myelin PC, but again, 16:0-18:1 turned over more rapidly than the other molecular species. Thus, within the same membrane, individual molecular species of a phospholipid class are metabolized at different rates. Comparison of our results with previous studies of turnover of molecular classes of phospholipids indicates that in addition to polar head group composition (Miller et al., 1977), fatty acid composition is very important in determining the metabolic fate of a phospholipid.

Animals↗