Cortisol effects on the glycosaminoglycan synthesis and molecular weight distribution in vitro

The effect of cortisol at different concentrations on the incorporation rate of [³H]glucosamine and [³⁵S]sulphate into glycosaminoglycans (GAGs) in human fibroblast culture medium was studied. The mol. wt distribution of the synthesized GAGs was determined by Sepharose 2B chromatography. Two sensitivity levels of GAGs to cortisol were observed: at a low cortisol concentration ( 1 × 10^?7 M) only the hyaluronic acid synthesis decreased and no changes were observed in the synthesis of sulphated GAGs or glycoproteins. At a high steroid concentration (1 × 10^?3 M) both the synthesis of hyaluronic acid and sulphated GAGs drastically decreased. The mol. wt distribution of medium GAGs did not change at cortisol concentrations 1 × 10^?9 M-1 × 10^?5 M. The possible role of cortisol in the metabolism of hyaluronic acid in vivo is discussed.     

The availability of inorganic sulphate as a rate limiting factor in the sulphate conjugation or xenobiotics in the rat?: Sulphation and glucuronidation of phenol

Phenol is converted by the rat in vivo into the sulphate and glucuronide conjugates. When the intravenously administered dose of ¹⁴C-labelled phenol was increased from 13 to 266 μmol/kg the percentage glucuronidated increased from 28 to 60 per cent of the dose; the percentage sulphated decreased from 72 to 40 per cent. In rats with intact kidneys the conjugates were almost completely excreted in the urine: when the kidneys were ligated phenylglucuronide was excreted in bile to a high extent, but biliary excretion of phenylsulphate was still very low. Using ³⁵S-labelled sodium sulphate, incorporation of [³⁵S]-sulphate into phenylsulphate could be observed; phenol enhanced the disappearance of [³⁵S]-sulphate from plasma. No significant depletion of inorganic sulphate was found when a high dose of unlabelled phenol (266 μmol/kg) was injected. The literature data on sulphate depletion by substrates of phenolsulphotransferase are critically reviewed; from our data is concluded that the relative decrease of phenol sulphation at high phenol doses is not due to sulphate depletion.     

The effect of drugs and secretagogues on the biosynthesis of gastric mucins.

Gastric mucosal glycoproteins were separated into three well-defined fractions: secreted mucin in vivo, adherent to cells, Fraction I; soluble mucin secreted during incubation in vitro, Fraction II; and a third, Fraction III released solely by pronase digestion (cell bound or intracellular mucin). ¹⁴C-U-D-glucose and ³⁵SO₄ incorporation into glycoprotein fractions II and III was studied during a 4-hr incubation period in vitro, of mucosal scrapings, freed from Fraction I, from rats treated in vivo, with secretin, histamine, aspirin and atropine. The effect of in vitro added puromycin and actinomycin was also studied. Secretin decreased and histamine increased the total amount of protein and glycoprotein in Fraction II. Histamine inhibited incorporation of glucose into this fraction, to a moderate extent. Secretin had no effect on incorporation. Per oral aspirin, administered for 15 min, decreased levels of secreted mucin Fraction I, and strongly inhibited glucose incorporation in Fraction III. Parenterally administered aspirin and atropine decreased mucin secretion in vivo (Fraction I) but activated glucose incorporation slightly in Fraction II and strongly in Fraction III. Puromycin and actinomycin added in vitro to the mucosal scrapings inhibited strongly glucose incorporation in Fraction III, but did not inhibit incorporation in Fraction II. This indicates the existence of two separate phases of mucin biosynthesis and secretion, both necessitating glucose incorporation, but only the first one being sensitive to puromycin and actinomycin. ³⁵SO₄ incorporation was strongly inhibited by all drugs studied. Sulphation of mucins appears to be much more sensitive to drug action than mucin biosynthesis itself. The above results indicate that the described system is suitable for the study in vitro of the time sequence and mechanisms of drug action.     

Effects of fasting, stress and drugs on gastric glycoprotein synthesis in the rat.

1 The relationship between gastric mucosal damage and synthesis of gastric glycoproteins, as measured by the rate of incorporation of N-acetyl-[3H]glucosamine, was investigated in rats after fasting and restraint stress and a single administration of aspirin (200 mg/kg, orally), phenylbutazone (200 mg/kg, orally), prednisolone (200 mg/kg, orally), or adrenaline (2 mg/kg, i.p.). In one experiment, the effects of aspirin and phenylbutazone on carbohydrate content of the glycoproteins were also determined. 2 Restraint stress, phenylbutazone and aspirin resulted in acute gastric mucosal erosions in some of the rats. Adrenaline produced severe sub-mucosal haemorrhage, but no erosions or ulceration, while prednisolone and fasting gave no gross pathology. 3 The rate of incorporation of N-acetyl-[3H]glucosamine into glycoproteins was decreased after all treatments except adrenaline. In the groups receiving restraint stress, aspirin or phenylbutazone, the decreases were more marked in rats which developed erosions than in those with no gastric pathology. 4 Aspirin and phenylbutazone also produced changes in the carbohydrate content of the glycoproteins, the effects again being greater in the rats which developed erosions. 5 The results are discussed in the context of a possible association between erosion formation and glycoprotein synthesis and it is proposed that inhibition of mucus glycoprotein biosynthesis may be one mode of action of stress and drugs in causing gastric mucosal damage.     

Effect of drugs which alter microsomal drug-metabolizing enzyme activity on rat hepatic cholesterol biosynthesis

Effects on cholesterol biosynthesis of compounds known to alter hepatic microsomal drug metabolism were assessed in rats in vivo by measuring the simultaneous incorporation of tracer quantities of [1-¹⁴C]acetate and ³H₂O into cholesterol. The incorporation of both substrates was increased with phenobarbital and decreased with CoCl₂ treatment. No change in incorporation of either substrate was noted when rats were treated with metyrapone, piperonyl butoxide or pregnenolone-16α-carboni-trile (PCN). The effect of these compounds on the assessment in vivo of cholesterol biosynthesis may be accurately characterized by use of either precursor as substrate. Compounds which induce or inhibit rat hepatic microsomal drug metabolism do not necessarily alter hepatic cholesterol biosynthesis.     

Oxidation of sodium sulphide by rat liver,lungs and kidney

Heparinized rat blood containing sodium [³⁵S]sulphide was perfused through isolated rat lungs, kidney or liver. The rate and extent of sulphide oxidation varied from one organ to another. In the isolated perfused lung system, [³⁵S]sulphide was oxidized slowly to [³⁵S]thiosulphate; only small amounts of [³⁵S]sulphate were delectable, possibly due to the absence of sulphide oxidase. In the isolated perfused kidney system, [³⁵S]sulphide was oxidized to [³⁵S]sulphate with [³⁵S]thiosulphate as a possible intermediate. In liver perfusion experiments [³⁵S]sulphide was oxidized rapidly and almost exclusively to [³⁵S]sulphate. The addition of unlabelled thiosulphate inhibited the formation of [³⁵S]sulphate and caused the release of [³⁵S]thiosulphate from the isolated liver. This suggests that thiosulphate is an intermediate in sulphide oxidation to sulphate. A mechanism for the rapid oxidation of sulphide to thiosulphate was shown to be present in rat liver mitochondria and, in the presence of glutathione, the thiosulphate was oxidized to sulphate. These results are discussed in relation to the contribution of lungs, kidney and liver to the oxidation of sulphide in vivo.     

Biochemical mechanisms of regulation of mucus secretion by prostaglandin E2 in rat gastric mucosa

The effects of prostaglandin E2 (PGE2) and inhibitors of RNA and protein synthesis on rat gastric mucosa were investigated in order to study the cellular and biochemical mechanisms involved in the PGE2-stimulated formation and secretion of gastric mucus. It was shown that PGE2 caused significant stimulation of gastric mucus secretion and this effect of PGE2 was inhibited by cycloheximide but not actinomycin D. The influence of PGE2 on the in vitro incorporation of N-acetyl-[3H]glucosamine and 14C-labelled amino acids in to the glycoproteins representing a major mucus component of the isolated gastric mucosa cells was also studied. The stimulatory effect of PGE2 on incorporation of labelled precursors into glycoproteins of gastric cells was also inhibited by cycloheximide. These results suggest that the effect of PGE2 on mucus production requires ongoing protein synthesis. cAMP can fully reproduce the effect of PGE2 on the formation and the secretion of gastric mucus. The binding of [3H]PGE2 to rat gastric non-parietal cell fractions consisting predominantly of mucoid cells correlated with the ability of PGE2 to increase adenylate cyclase activity in these cells. PGE2 had no effect on adenylate cyclase activity in cell suspensions enriched in parietal cells. These data suggest further that the stimulatory effect of PGE2 on mucus secretion may be mediated by cAMP as a messenger.     

Some factors regulating [1-14C] acetate incorporation into aflatoxins by spheroplasts and spheroplast lysates from Aspergillus parasiticus

Factors regulating aflatoxin biosynthesis were studied in spheroplasts and lysates of Aspergillus parasiticusNRRL 3240. Over a 2 hr period, ribose, sucrose and maltose stimulated the incorporation of [1-¹⁴C] acetate into aflatoxins. Of a number of inorganic salts studied, zinc sulphate, magnesium sulphate, cobaltous chloride, cadmium acetate and strontium chloride stimulated the incorporation of labeled acetate into aflatoxins. Vanadyl sulphate and ferrous sulphate inhibited de novo aflatoxin formation in spheroplast lysates. Strontium chloride at concentrations of 0·01–0·5 mM stimulated [1-¹⁴C] acetate incorporation. Silver nitrate, copper sulphate and chlorides of manganese, calcium and barium markedly stimulated the incorporation of radioactivity into aflatoxins. An inverse correlation between the incorporation of [1-¹⁴C] acetate into aflatoxins and lipids was noted. In lysates, addition of pyruvic acid markedly increased de novo aflatoxin synthesis. Acetoacetate and bicarbonate enhanced incorporation of radioactivity at lower concentrations. Citric acid at 1–10 mM concentrations was stimulatory to incorporation of label into aflatoxins while malonic acid was inhibitory. In lysates, EDTA enhanced acetate incorporation into aflatoxins and inhibited incorporation of label in intact spheroplasts. This effect was only partially reversed by the addition of ZnSO₄ or MgSO₄.     

Alterations in [3H]thymidine incorporation into DNA and [3H]uridine incorporation into RNA induced by 5-azacytidine in vivo.

Administration in vivo of 5-azacytidine (5-aza-CR) caused suppression of [³H]thymidine ([³H]TdR) incorporation into DNA of bone marrow and gastrointestinal mucosa of mice and a more prolonged suppression of L1210 ascites tumor. Single doses of 5-aza-CR caused a modest and short-lived suppression of incorporation of [³H]uridine ([³H]UR) into nuclear RNA of L1210 ascites tumor cells. No suppression of [³H]UR incorporation into RNA of bone marrow or gastrointestinal mucosa was observed. L1210 tumor cells resistant to the other active cytidine analogue, cytosine arabinoside, demonstrated less disruption of [³H]TdR incorporation after exposure to 5-aza-CR, suggesting some cross resistance in the effects of these two drugs on DNA synthesis. Survival studies carried out in mice bearing both the sensitive and resistant L1210 tumor cell lines confirmed cross resistance of the anti-tumor effects of the two cytidine analogues. Second doses of 5-aza-CR, with the timing og administration based upon the differing patterns of recovery of [³H]TdR incorporation between normal tissues and tumor cells, led to a prolongation of survival in mice bearing the sensitive L1210 ascites tumor.     

Effects of a membrane sugar analogue, 6-deoxy-6-fluoro-d-galactose,on the L1210 leukemic cell ectosialyltransferase system

In L1210 leukemia cells, 6-deoxy-6-fluoro-d-galactose specifically inhibited the incorporation of [³H]-d-galactose, while that of other precursors of glycoconjugate biosynthesis, including mannose and glucosamine, was unaffected. The activation of [6-³H]-6-deoxy-6-fluoro-d-galactose to a nucleotide sugar was similar to that found for [³H]-d-galactose. The incorporation of either sugar after 1 hr was visualized by electron microscopic autoradiography to be in the Golgi region. Treatment of L1210 cells with 6-deoxy-6-fluoro-d-galactose in vitro or in vivo resulted in a specific, dose- and time-dependent decrease in the activity of cell surface sialyltransferase (ectosialyltransferase) but not of 5′-nucleotidase, a plasma membrane marker enzyme. The decrease in ectosialyltransferase activity appeared to be selective and is suggested to be due to structural modification of the cell surface galactoprotein acceptors for this enzyme. The data indicate that 6-deoxy-6-fluoro-d-galactose is an effective modifier of cellular glycoconjugate in that its incorporation into certain cell surface components results in a modification of plasma membrane structure and function.     

Synergistic effect of 5-fluorouracil and N-(phosphonacetyl)-l-aspartate on cell growth and ribonucleic acid synthesis in a human mammary carcinoma

The biological effects of $\text{N-(}\text{phosphonacetyl}\text{)-}\text{l}\text{-}\text{aspartate}$ (PALA) and 5-fluorouracil (5-FU) were examined singly, and in combination, on the growth of a human mammary carcinoma (MDA) cell line in culture. All combinations of 5-FU (2.5 × 10^?7 to 1.5 × 10^?5M) and PALA (6.0 × 10^?5 to 3.6 × 10^?3 M) resulted in synergistic inhibition of cell growth as revealed by a 50 per cent isobologram.To examine the biochemical basis for the synergism, measurements of the incorporation of [³H]-5-FU into total non-poly(A)- and poly(A)-RNA, and of the simultaneous incorporation of [¹⁴C]deoxyguanosine and [³H]deoxyuridine into DNA, were determined. The combination of 3.7 × 10^?5M PALA and 1 × 10^?6 M 5-FU produced 65–85 per cent inhibition of cell growth after continuous treatment for 13 days. Treatment of the cells for 3 or 24 hr with the same drug regimen produced approximately a 170 per cent increase in the incorporation of 1 × 10^?6M [³H]-5-FU into poly(A)RNA in comparison to [³H]-5-FU treatment alone; exposure for 24 hr to 3.7 × 10^?5 M PALA and 1 × 10^?6 M [³H]-5-FU resulted in a 285 per cent increase in the incorporation of [³H]-5-FU into non-poly(A)RNA. The incorporation of either [¹⁴C]deoxyguanosine or [³H]deoxyuridine into DNA was not inhibited by this drug regimen; however, the incorporation of [³H]deoxyuridine into DNA was elevated significantly upon 12 or 24 hr of exposure to PALA alone. PALA and 5-FU treatment resulted in a 75 per cent reduction in the concentration of UTP and no change in the concentration of 5-fluorouridine-5′triphosphate 5-FUTP) versus 5-FU treatment alone. Thus, the proportion of 5-FUTP in the total 5FUTP + UTP pool was enhanced more than 3-fold by the combination regimen. These results indicate that the synergistic effect of the combination of PALA and 5-FU on the growth of MDA cells correlates with an increased proportion of 5-FUTP in the pyrimidine nucleotide pool and, consequently, with an enhanced incorporation of 5-FU into RNA, but not with inhibition of DNA synthesis.     

Analysis of the actions of the novel dopamine receptor-directed compounds (S)-OSU6162 and ACR16 at the D2 dopamine receptor

BACKGROUND AND PURPOSE

The two phenylpiperidines, OSU6162 and ACR16, have been proposed as novel drugs for the treatment of brain disorders, including schizophrenia and Huntington''s disease, because of their putative dopamine stabilizing effects. Here we evaluated the activities of these compounds in a range of assays for the D₂ dopamine receptor in vitro.

EXPERIMENTAL APPROACH

The affinities of these compounds for the D₂ dopamine receptor were evaluated in competition with [³H]spiperone and [³H]NPA. Agonist activity of these compounds was evaluated in terms of their ability to stimulate [³⁵S]GTPγS binding.

KEY RESULTS

Both compounds had low affinities for inhibition of [³H]spiperone binding (pK_i vs. [³H]spiperone, ACR16: <5, OSU6162: 5.36). Neither compound was able to stimulate [³⁵S]GTPγS binding when assayed in the presence of Na⁺ ions, but if the Na⁺ ions were removed, both compounds were low-affinity, partial agonists (E_max relative to dopamine: ACR16: 10.2%, OSU6162:54.3%). Schild analysis of the effects of OSU6162 to inhibit dopamine-stimulated [³⁵S]GTPγS binding indicated Schild slopes of ∼0.9, suggesting little deviation from competitive inhibition. OSU6162 was, however, able to accelerate [³H]NPA dissociation from D₂ dopamine receptors, indicating some allosteric effects of this compound.

CONCLUSIONS AND IMPLICATIONS

The two phenylpiperidines were low-affinity, low-efficacy partial agonists at the D₂ dopamine receptor in vitro, possibly exhibiting some allosteric effects. Comparing their in vitro and in vivo effects, the in vitro affinities were a reasonable guide to potencies in vivo. However, the lack of in vitro–in vivo correlation for agonist efficacy needs to be further addressed.     

Renal Excretion of some Aryl Sulphate Esters in the Rat

The renal clearance of inulin, phenyl [³⁵S]sulphate, naphthyl 2-[³⁵S]-sulphate and 2-hydroxy-5-nitrophenyl [³⁵S]sulphate was measured at various plasma concentrations in the rat.

A considerable proportion of each ester was bound to plasma proteins in vivo and the ratio of ³⁵S-labelled sulphate ester/inulin clearance demonstrated that all three esters are secreted by the renal cells.

The contribution of the renal secretory process to the overall urinary excretion ranged between 22–59% (phenyl [³⁵S]sulphate), 58–87% (naphthyl 2?[³⁵S]sulphate) and 60–72% (2-hydroxy-5-nitrophenyl [³⁵S]sulphate).

These findings are discussed in relation to the detoxication of phenols by sulphate conjugation.     

Aspirin, Prostaglandins and mucopolysaccharide/glycoprotein secretion

The object of the present study was to investigate the possibility that the ulcer-protective action of prostaglandins (PGs) in eliciting mucus discharge in the stomach could be due to their effect in enhancing the biosynthesis of mucus. Intraperitoneal injection of 2,5 mg/kg PGE2, or the same dose of PGE2 plus 200 mg/kg aspirin (p.o.), both failed to cause any statistically significant changes in the incorporation of radioactive sulphate into gastric mucus glycoproteins in vivo compared with controls. Aspirin, under these conditions, inhibits mucus synthesis in this effect may be related to the development of gastric mucosal damage by this drug. In contrast, PGE2 administration reverses the gastric mucosal damage induced by aspirin so that the ulcer-protective effect of PGE2 appears to be unrelated to mucus synthesis. PGE2 (0.125 - 1.25 microgram/ml) inhibited oxygen consumption and 14CO2 output from 1-14C, and 6-14C glucose in rat gastric mucosal slices in vitro. Thus the absence of effect of PGE2 on mucus biosynthesis may be due to an effect of this PG in reducing the capacity of the mucosa to yield energy (ATP) from the metabolism of glucose.     

Effect of neuroleptics on indoleamine-N-methyltransferase activity and brain metabolism of bufotenin

A range of neuroleptics, non-neuroleptic phenothiazines and antidepressants were tested for their ability to inhibit purified rabbit lung indoleamine-N-methyltransferase (INMT) and to modify the metabolism of [³H]bufotenin administered intraventricularly. Benperidol and droperidol proved to be the most potent inhibitors of INMT among the compounds tested. On the other hand trifluperidol and haloperidol showed no inhibitory activity at concentrations up to 2.5 mM, while chlorpromazine, thioridazine, pericyazine and perphenazine were effective only at 250 μM or 2.5 mM. Oxidative deamination was shown to be an important pathway in normal rat brain for the metabolism of bufotenin. Of the drugs tested only chlorpromazine elevated the brain [³H]bufotenin/[³H]-5-HIAA ratio whereas pimozide and thiothixene caused a decrease. These findings suggest that neuroleptic drugs in general do not exert their anti-psychotic effects by inhibiting the synthesis or accelerating the oxidative deamination of N,N-dimethylated indoleamines.     

Inhibition of gastrointestinal mucosal glycoprotein synthesis by the β-adrenergic blocking drug,practolol

The effect of administration of practolol and other β-blocking agents on gastrointestinal mucosal glycoprotein synthesis was studied in the rat. Practolol, at a dose of 50 mg/kg, inhibited the incorporation of N-acetylglucosamine into gastric mucosal glycoproteins, while acebutolol, atenolol, pronethalol and propranolol had no inhibitory effect, even at a dose of 200 mg/kg. In addition, practolol inhibited the incorporation of N-acetylneuraminic acid, D-fucose and L-serine into gastric mucosal glycoproteins, while the other β-blocking agents had no effect. Administration of practolol caused no significant change in the rate of incorporation of glycoprotein precursors into intestinal mucosal glycoproteins. These results indicate that of the β-blocking drugs studied, inhibition of glycoprotein synthesis is associated only with practolol and is independent of its β-blocking effect.     

Effect of a new potent H2-receptor antagonist 3[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-N2-sulfamoylpropionamidine (YM-11170) on gastric mucosal histamine-sensitive adenylate cyclase from guinea pig

The effect of 3[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-N²-sulfamoylpro-pionamidine (YM-11170), a new thiazole H₂-receptor antagonist bearing propionamidine at the terminus of a side chain, on histamine-sensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] of gastric mucosa from the guinea pig was studied and compared with that of cimetidine. YM-11170 displaced the concentration-stimulation curve of histamine-sensitive adenylate cyclase to the right with a pA₂ of 7.65 (K_i, = 2.25 × 10^?8M). Stimulation of gastric adenylate cyclase by 0.1 mM histamine was competitively inhibited by YM-11170 and cimetidine in a dose-dependent manner, with ic₅₀ values of 5.9 × 10^?7M and 1.4 × 10^?5M respectively. Hippocampal histamine-sensitive adenylate cyclase in the presence of 0.1 mM histamine was also competitively inhibited by YM-11170 with an ic₅₀ of 1.1 × 10^?7 M. YM-11170 did not affect Gpp(NH)p-, NaF-, PGE₂-stimulated or basal activity of the gastric adenylate cyclase. These data, together with other results, indicate that YM-11170 is a highly selective and potent H₂-receptor antagonist which competes with histamine at the receptor site on the histamine-sensitive adenylate cyclase.     

Biochemical effects of d-tetrandrine and thalicarpine.

The benzylisoquinoline alkaloids d-tetrandrine and thalicarpine inhibit the biosynthesis of DNA, RNA and proteins, when incubated with S180 cells in vitro. Oxidation of glucose[¹⁴C] to ¹⁴CO₂ was not affected by either alkaloid at levels up to 100 μg/ml in vitro. Incorporation of labeled acetate into lipids was inhibited only by thalicarpine at 100 μg/ml. Inhibition of the incorporation of thymidine into DNA was also observed in vivo after treatment with these drugs at 30–120 mg/kg; under these conditions, the synthesis of RNA and protein was not inhibited. In an attempt to elucidate the mechanism for inhibition of nucleic acid synthesis, the interaction of DNA, RNA and polynucleotides with the alkaloids was studied by gel filtration and dialysis. The two drugs associated with both DNA and RNA, but exhibited different affinities for the five polynucleotides examined. Both alkaloids were bound by polyguanylic and polyadenylic acids, but whereas d-tetrandrine associated only poorly with polythymidylic acid and not at all with polyuridylic acid, it was polycytidylic acid that showed no affinity for thalicarpine.     

Effect of polychlorinated biphenyls (PCBs) administration on phospholipid biosynthesis in rat liver

The effect of PCBs or phenobarbital on the biosynthesis of phospholipids in hepatic endoplasmic reticulum of rats was studied by the intraperitoneal injection of [³²P]orthophosphate, [Me?¹⁴ C]choline or [2?³H]glycerol. Significant increases in liver microsomal phospholipid content after the administration of either PCBs or phenobarbital indicated the actual proliferation of endoplasmic reticulum membranes. The rate of both [³²P] and [¹⁴C] incorporations into microsomal choline-containing phospholipids, such as phosphatidylcholine, sphingomyelin and lysophosphatidylcholine, was reduced to one fifth by PCBs administration compared with control animals. The incorporation of [³²P]orthophosphate into phosphatidylethanolamine or other phospholipid classes was less or not affected, respectively, by PCBs administration. The specific inhibitory effect of PCBs on the incorporation into cholinecontaining phospholipids was not observed when [2?³-H]glycerol was used as a precursor. Phenobarbital administration, however, increased significantly the rate of [³²P] incorporation into liver phospholipids, especially phosphatidylcholine. It is suggested that the increase in microsomal phospholipid content by PCBs administration is not due to the stimulation of synthesis but to the inhibition of the catabolism of membrane phospholipids and that the increase in content caused by phenobarbital is due at least in part, to the stimulation of synthesis. The possible site(s) of PCBs-induced inhibition of phospholipid biosynthesis in rat liver is discussed.     

The Biodegradation of the Surfactant Undecyl Sulphate

1. The metabolism of the odd-numbered carbon chain surfactant, potassium undecyl [³⁵S]sulphate. in the rat was investigated.

2. The major route for elimination of radioactivity was the urine, regardless of the route of administration.

3. The surfactant was extensively degraded in vivo to yield propionic acid 3-[³⁵S]sulphate, the major radioactive component in urine. A second urinary metabolite was identified tentatively as pentanoic acid 5-[³⁵S]sulphate.

4. Whole-body autoradiography revealed the liver as the major site of metabolism.

5. The nature of the metabolic products of undecyl sulphate suggest that it is bio-degraded by initial ω-oxidation followed by β-oxidation.