Comparative biochemistry and physiology. C: Comparative pharmacology最新文献

1. The possible involvement of eicosanoids, cyclic adenosine monophosphate (c-AMP), and inositol 1,4,5-trisphosphate (IP₃) in serotonin-(5-hydroxytryptamine-) induced secretion in rat ileum in vivo was studied.

2. Serotonin caused a significant increase in mean Ip₃ levels. Indomethacin reduced serotonin-induced secretion of water by 28%. Thus, Ip₃ and eicosanoids appear to be intracellular mediators of serotonin-induced secretion in rat ileum.

3. Serotonin, BRL 24924, and cisapride all inhibited theophylline-induced increases in c-AMP concentrations in rat ileal segments. Neither BRL 24924 nor cisapride caused any change in Ip₃ levels.

4. These data suggest that a 5-HT₂ receptor dependent on Ip₃ and eicosanoids is involved in mediating in serotonin-induced secretion in rat small intestine.

1. The metabolism of di-, tri- and tetrabromobiphenyls (PBBs) by hepatic microsomes isolated from control animals and animals treated with Arochlor 1254 was studied.

2. Hepatic microsomes isolated fom control rats expressed higher rates of oxidations than avians

3. Treatment of rats and pigeons with Arochlor 1254 induced cytochrome P450 dependent monooxygenases leading to an increased regioselective metabolism of PBB isomer and congeneres.

4. There was an inverse relationship between the degree of halosubstitution and microsomal oxidation. Meta-para carbon atoms free of halosubstitution were the preferred side for oxidation.

1. The lipid and amino acid composition of the mussel Pseudoanodonta complanata, collected from two locations in Danube river with different pollution, was investigated.

2. The water pollution causes radical changes in the lipid and amino acid composition of the mussel, which can be interpreted as disturbances of some metabolic processes as well as adaptation towards pollution. These changes can be used in future for monitoring.

1. High concentration of ammonia (13.5 and 23.3 mM) was effective for maintenance of normal morphology of cultured eel hepatocytes.

2. Synthesis of urea did not increase by addition of ammonia to eel hepatocytes.

3. Intracellular protein content in hepatocytes cultured with ammonia was higher than that in control cells.

4. Consumption of essential amino acids, especially Thr, Val, Ile, and Lys, in the medium was reduced by addition of ammonia.

5. A Glu-derivative was synthesized by cultured hepatocytes. The amount of the derivative in the medium was the highest next to that of Gly and increased as the concentration of ammonia in the medium increased.

6. Specific activity of glutamate dehydrogenase (GDH) in cultured hepatocytes increased as the concentration of ammonia increased and the activity of GDH in hepatocytes cultured in the presence of 23.3 mM ammonia was 2.6 times higher than that in the control cells.

Chemically synthesized bovine thymopoietin I (TPO-I) and thymopoietin II (TPO-II) were evaluated as inhibitors of ¹²⁵I α-Bungarotoxin binding to rat brain neural membranes and found to be over 1,000 × less potent ($\text{IC}{}_{50}\text{= 10μ}\text{M}$) than reported for thymopoietin isolated from bovine thymus.

1. Sterol composition of the aboral body-wall of male specimens of Asterias rubens starved for three weeks, was compared with that of male sea stars which during the starvation period had been exposed to cadmium (100$\text{μg}\text{l}$).

2. Sterol composition of non-exposed animals appeared to be constant as assessed over a period of four years.

3. Cadmium-exposure strongly influenced sterol composition. The effect was related to the reproductive cycle, effects being different in the spermatogenic and the aspennatogenic phase.

4. Effects on total C₂₇-, C₂₈-,Δ^7.22-, and some individual sterols showed abrupt changes in November and March, coinciding with the start and the end of the reproductive cycle.

5. In one experiment additional parameters were determined. Cadmium-exposure resulted in a significant increase of polar lipids in the body-wall and a decrease of the sterol/phospholipid ratio. The increase of polar lipids was accompanied by a decrease of C₂₈-sterols. Consequences for viscosity are discussed.

6. Cadmium-exposure also resulted in a decrease of phosphatidylserine and an increase of phosphatidylethanolamine.

1. Long-term exposure (16 weeks) of the American eel, Anguilla rostrata, to an environmentally realistic concentration of cadmium (150 $\text{μg}\text{l}$) causes a chronic elevation of plasma cortisol. During this time span, the eels retain the ability to respond to a weak additional stress (CO₂ bubbles for 1 min) with a further increase in plasma cortisol.

2. Plasma glucose levels are significantly lowered after two weeks of exposure to cadmium (75 and 150 $\text{μg}\text{l}$). However, subsequently they return close to control levels.

3. It is concluded that (a) a moderate cadmium pollution of the eel's habitat suffices to cause chronic stimulation of the eel's adrenocortical axis, and (b) the resulting continued hypereortisolemia must seriously affect the eel's metabolism, immunosystem, gonadal maturation, and ability to migrate to its spawning grounds.

1. Comparative studies of β-N-acetylglucosaminidase (NAG, EC 3.2.1. 52) and β-galactosidase (EC 3.2.1.23) activities, protein concentration and creatinine clearance, were carried out in urine and kidney from guinea pigs treated with “toxic oil”, orally administered under different conditions, related to controls.

2. Enzyme activities did not vary significantly in urine with any of the studied conditions of oil administration. By contrast, in kidney, β-d-galactosidase disclosed a significant increase in all the treatments studied when compared to controls without treatment.

3. Urinary protein excretion, creatinine concentration and creatinine clearance were significantly greater in treated animals than in controls after 4 weeks of treatment.

4. Relative kidney weight ($\text{g}\text{100}$ g body wt), was significantly lower in animals treated for 28 days with previously heated oil.

1. A variety of structurally dissimilar polyhalogenated cyclic hydrocarbons produce similar toxic effects. The molecular mechanisms involved in the production of these toxic manifestations is not known.

2. We have proposed that reactive oxygen species may be involved, and have therefore examined the time-dependent effects of lindane (30$\text{mg}\text{kg}$), DDT (40 $\text{mg}\text{kg}$), chlordane (l 20 $\text{mg}\text{kg}$), and endrin (4.5 $\text{mg}\text{kg}$) on the production of hepatic mitochondrial and microsomal lipid peroxidation and DNA single strand breaks, two indices of oxidative stress.

3. All four xenobiotics resulted in significant increases in hepatic lipid peroxidation and DNA damage. Earliest (6 hr) increases in both lipid peroxidation and DNA damage were observed following lindane adminstration. Time-dependent increases in both parameters were observed following endrin administration.

4. Maximum increases in DNA single strand breaks of 2.8- and 2.5-fold were observed 12 hr after DDT and chlordane administration, respectively, while a 4.4-fold increase was observed 24 hr after endrin adminstration.

5. The results demonstrate that the four structurally dissimilar polyhalogenated hydrocarbons produce oxidative tissue damage which may contribute to the toxic manifestations of these xenobiotics, and exhibit different toxicokinetic properties.

1. Using immunocytochemical techniques and confocal scanning laser microscopy, the proteocephalidean cestode, Proteocephalus pollanicola from Lough Neagh pollan (Coregonus autumnalis) was examined for the presence of the native platyhelminth neuropeptide, neuropeptide F (NPF).

2. An antiserum specific for whole-molecule NPF(1–39) (Moniezia expansa) did not immunostain nerve processes in P. pollanicola. A C-terminally-directed NPF(30–39) (M. expansa) antiserum immunostained nerve fibres and cell bodies of both the central and peripheral nervous systems, including innervation associated with the female reproductive system.

3. The pattern of immunoreactivity was identical to that obtained using antisera to the C-terminal region of mammalian NPY-superfamily peptides and the invertebrate neuropeptide, FMRFamide.

4. Under radioimmunoassay conditions, only the C-terminally-directed NPF antiserum cross-reacted with the P. pollanicola peptide and detected 58.74 $\text{ng}\text{g}$ wet weight of NPF-IR in extracts of the worm.

5. Chromatographic characterisation of P. pollanicola NPF-immunoreactivity indicated an apparent molecular weight of 4400–4700 Da, similar to that of NPF (M. expansa).

6. Further analytical HPLC characterisation identified two molecular forms of P. pollanicola NPF-immunoreactivity, both of which had different retention times from those of NPF (M. expansa) and NPF (Artioposthia triangulata).

7. These data suggest that P. pollanicola possesses a neuropeptide which is homologous in its C-terminal region to NPF (M. expansa) but diners in its mid- to N-terminal region.