1. Microsomal monooxygenase systems which contain cytochrome P-450 forms as their active centres are found in birds, reptiles and amphibians. Liver provides a rich source of monooxygenases but they are also present in other tissues. 2. In the hepatic microsomes of these species, levels of cytochrome P-450 and, in most cases monooxygenase activities, are lower than are found in hepatic microsomes of mammals. 3. Amongst birds, the lowest hepatic microsomal monooxygenase activities have been reported for specialized predators (fish-eaters and raptors). 4. When birds are dosed with inducers of the 3-methylcholanthrene (MC) type, the pattern of induction is similar to that in mammals. In contrast, phenobarbitone-type inducers are less effective in birds than in mammals--in some cases having no action at all. Prochloraz is a stronger inducer in birds than in the rat; it is an inducer of mixed type in birds. 5. Partial purification of avian cytochromes P-450 indicates substantial differences in properties from those of mammals. Further differences between birds and mammals in regard to the immunochemical properties of isoforms are evident from comparative studies using Western blotting. 6. On the evidence of Western blotting and response to inducers, cytochromes of family II (P450 II) seem less well represented in birds than in mammals. 7. The low monooxygenase activities of certain species of birds may make them relatively susceptible to lipophilic environmental chemicals that are detoxified by this system.

Amphibians↗

PubMed1989

Cytochromes P-450 of sea birds: cross-reactivity studies with purified rat cytochromes.

1. Polyclonal antibodies against rat cytochrome P-450c (IA1), P-450d (IA2), P-450b (IIB1), P-450h (IIC11) and P-450j (IIE1), were used to probe liver microsomes prepared from six sea bird species collected from the Irish Sea between 1978 and 1988. 2. Significant cross-reactivity in all the sea bird species was seen only with antibodies to P450 IA1. Expression of cross-reactivity proteins was highly variable between individual birds, which show evidence of environmental induction. 3. Shared epitopes to P450 IA1 and IA2 were seen on a single protein expressed in liver microsomes from the cormorant (Phalacrocorax carbo). 4. Antibodies against members of rat P450 gene family II showed a small degree of cross-reactivity with sea bird microsomes. Antibodies against P450 IIB1 and IIC11 showed weak cross-reactivity in all species with little inter-individual variation. Antibodies to P450 IIE1 showed no cross-reactivity in any bird species. 5. P450 gene family I appears to be well represented in sea birds while P450 gene family II is not well developed in this group of lower vertebrates.

Animals↗

PubMed1988

Multiple forms of sheep serum A-esterase activity associated with the high-density lipoprotein.

Five lipoproteins of sheep serum expressing A-esterase activity, but with differing activities towards four organophosphate substrates, were separated by a combination of gel filtration and ion-exchange chromatography. Each had an Mr of approx. 360,000 and contained a major peptide of Mr 28,000-30,000 that appeared to be present as several isoforms on urea/agarose isoelectric focusing. In every case this peptide split into a number of bands on urea/agarose isoelectric focusing. The bands appear to represent isoforms of the peptide, and four lipoproteins yielded characteristic patterns of bands. This peptide resembles the apolipoprotein A-I of human serum, and available evidence suggests that this is the protein that expresses A-esterase activity. Evidence is presented for the existence of different species of high-density lipoprotein HDL2 particles containing different complements of peptide isoforms and expressing contrasting substrate specificities towards organophosphates.

Animals↗

PubMed1988

Avian esterases as indicators of exposure to insecticides--the factor of diurnal variation.

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Animals↗

PubMed1988

Influence of thyroid states on stress gastric ulcer formation.

Thyroid hormones exert a critical developmental and regulatory role on the morphology and biochemistry of gastrointestinal mucosal cells. However, the relationship between thyroid function and stress gastric lesion formation remains undetermined. This study was designed to test the hypothesis that thyroid states may affect the acute development of gastric lesions induced by cold-restraint stress. Normal (euthyroid), hyperthyroid (200 micrograms of T4 i.p. x 7 days) and hypothyroid (thyroidectomized) rats were used. Gastric lesion incidence and severity was significantly (p less than 0.05) increased in hypothyroid rats, whereas in contrast hyperthyroid rats developed significantly less gastric lesions. As anticipated, plasma levels of thyroxin (T4) were significantly (p less than 0.01) elevated in hyperthyroid rats, and undetectable in hypothyroid rats. Acute pretreatment with i.p. cimetidine (100 mg/Kg), but not T4 (200 micrograms/Kg) 1 h prior to stress completely prevented gastric lesions formation in hypothyroid rats. Finally, binding of 3H-dihydroalprenolol to beta-adrenergic receptors on brain membranes prepared from frontal cortex was reduced by 20% in hypothyroid rats after 3 h of stress. These and other data contained herein suggest that thyroid hormones contribute to modulate the responsiveness of the gastric mucosa to stress. The increased rate of ulcerogenesis observed in hypothyroid rats appears to be mediated by gastric acid secretion. The central mechanism of this response may involve decreased brain nonadrenergic receptor function.

Animals↗

PubMed1988

Chronic alcohol ingestion decreases pituitary-thyroid axis measures in Fischer-344 rats.

In a chronic feeding study adult male Fischer-344 rats (n = 12) were fed a nutritionally complete liquid diet containing 10% (w/v) ethanol for 40 days while control animals (n = 12) were pair fed a nutritionally complete isocaloric diet in which dextrose was substituted for ethanol. Treated animals were gradually introduced to and withdrawn from the 10% diet. At the end of the study and at sacrifice ethanol-fed rats had gained slightly more weight than pair-fed controls. They also showed a significant decrease in total thyroxine, free thyroxine, L-triiodothyronine, reverse L-triiodothyronine, and basal thyroid-stimulating hormone. These differences did not appear to result from caloric deprivation alone. Possible explanations for some of these thyroidal changes are discussed.

Alcoholism↗

PubMed1988

'....officiously to keep alive'.

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Aborted Fetus↗

PubMed1987

Dopamine receptors in human gastrointestinal mucosa.

Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using 3H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of 3H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. Binding parameters obtained from the regression lines of the Scatchard plots of gastric mucosa of males were Bmax = 73.4 +/- 4.0 pmoles/mg protein; KD = 154 +/- 20 nM and Bmax = 95 +/- 13.6 pmoles/mg protein and KD = 826 +/- 200 nM in females. In duodenal mucosa of males these parameters were Bmax = 63.9 +/- 15.9 pmoles/protein; KD = 235 +/- 53 nM and Bmax = 83.2 +/- 19.4 pmoles/mg protein; KD = 568 +/- 104 nM in females. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine↗

PubMed1987

Distinction between 'A'-esterases and arylesterases. Implications for esterase classification.

'A'-esterase activities (substrates paraoxon and pirimiphos-methyloxon) and arylesterase activities (substrate phenyl acetate) were assayed in the sera of 14 species of birds representing seven different orders and 11 species of mammal representing five different orders. Ten species of birds had no detectable 'A'-esterase, and the remaining four species only low activity, yet all birds showed considerable arylesterase activity (16.8-99.3 mumol/min per ml of serum). Ten species of mammal showed both 'A'- and 'aryl'-esterase activities. In humans, gel filtration of serum completely separated peaks representing paraoxonase and arylesterase activities. Thus, in both birds and humans, serum enzymes exist that express arylesterase activity but not 'A'-esterase activity. These findings suggest that a distinction should be made between these two types of esterase in future classifications.

Animals↗

PubMed1987

"A" esterases and their role in regulating the toxicity of organophosphates.

Esterases which can hydrolyse organophosphates without being inhibited by them are termed "A" esterases. Using paraoxon and pirimiphos-methyl oxon as substrates, high "A" esterase activity is found in the liver and plasma or serum of a range of mammalian species. In a study of serum "A" esterases of sheep and humans, over 80% of the activity separated into the high density lipoprotein (HDL) fraction following ultracentrifugation. When HDL fractions from sheep serum were run on Sepharose gel columns, most of the paraoxonase activity separated as a single peak of estimated molecular weight 360,000, which corresponds to that of HDL2 of humans. During the course of purification of "A" esterases by three different column procedures, contrasting esterase elution profiles were obtained with organophosphate and pyrethroid substrates. This was strong evidence for the existence of multiple forms of HDL "A" esterases. Levels of "A" esterase activity in plasma and liver of birds were much lower than those of mammals. This appears to be the main reason why birds are much more susceptible than mammals to organophosphates such as pirimiphos-methyl and diazinon which form active oxons that are good substrates for mammalian "A" esterases. No "A" esterase was detected in strains of rust red flour beetle (Tribolium castaneum) which were resistant to organophosphates. Similar observations have been made with strains of other insects resistant to organophosphates, raising the question to what extent esterases of this type are present in insects.

Animals↗

PubMed1987

Bioaccumulation in food chains--a rational approach.

How much and how quickly pollutants move along food webs is an important part of predicting ecological effects. Animal size and comparative metabolism are two important aspects that have been mostly ignored.

Animals↗

PubMed1987

Kinetic models for predicting bioaccumulation of pollutants in ecosystems.

Steady state kinetic models, which may be useful for the prediction from simple data, of the bioaccumulation of liophilic pollutants in ecosystems are discussed. For some aquatic species, such as Mytilus edulis, bioconcentration factors (BCFs) are closely related to water solubilities, and octanol: water partition coefficients (Kows). In other cases, more complex models are necessary to take account of metabolism and/or uptake from food. Somewhat different considerations apply in the estimation of bioaccumulation factors (BFs) for terrestrial organisms that cannot excrete lipophilic compounds by diffusion into ambient water. The relationship between half-lives and BFs is discussed. Metabolism is necessary for the effective elimination of lipophilic pollutants by terrestrial animals, and a model is proposed for the prediction of BFs from kinetic data obtained from in vitro metabolism studies. If such a model can be successfully developed it will make possible the prediction of bioaccumulation of pollutants by a wide range of species which cannot be studied by present methods.

Journal Article↗

PubMed1987

GABA uptake is inhibited by thyroid hormones: implications for depression.

Studies of the effects of thyroid hormones on the uptake of neurotransmitters by homogenates of rat cerebral cortex have revealed a significant competitive inhibition of neuronal uptake of [3H]GABA by thyroid hormones (T3 greater than T4 greater than rT3). The IC50 for inhibition of GABA uptake by T3 was estimated at 4 microM and that of T4 at 11 microns. GABA uptake in homogenates of cerebral cortex from hypothyroid rats was significantly enhanced over that of controls; however, uptake in tissues from hyperthyroid rats was not significantly diminished.

Animals↗