Comparative biochemistry and physiology. Part C, Pharmacology, toxicology & endocrinology最新文献

Dopamine administered continuously through osmotic pumps altered the PHA wattle response and in vitro leukocyte capillary tube migration in UNH 105 chickens. The PHA wattle response was suppressed significantly by 48 hr exposure to dopamine at a dose of 1 microgram/hr. Administration of 10 micrograms/hr dopamine for 48 hr enhanced significantly in vitro leukocyte migration.

Glucagon, dibutyryl cAMP (Bt2cAMP) and 8-(4-chlorophenylthio) cAMP (CptcAMP), singly or when combined, stimulated tyrosine aminotransferase (TAT) activity in 17-day-old chick embryos in ovo. Maximal induction was produced within 4 hr of injection of the inducers. The effects of glucagon and the cAMP analogues were not additive. Glucagon administration was accompanied by a rapid increase in hepatic cAMP concentration which remained elevated for at least 4 hr. The stimulated increase in TAT activity elicited by the hormone or cyclic nucleotide was prevented by injection of cycloheximide or cordycepin. These results are discussed vis-à-vis the possible regulation of TAT in ovo by physiological concentrations of glucagon and the likely role of cAMP as a second messenger in this process during chick embryogenesis.

A major component of the cellular stress response entails the induced synthesis of a suite of stress proteins under environmentally adverse conditions that functions to protect organisms from environmentally induced damage. Here, we examined induction of the stress response in the embryos of the sea urchin Strongylocentrus purpuratus under a combination of environmentally realistic conditions. First, we examined the response elicited over a range of free cupric ion activities, (Cu2+), using a metal buffer system to control trace metal speciation. We observed no pronounced differences in translational patterns in embryos exposed to free cupric ion activities, (Cu2+), of 10(-13)-10(-9) M by metabolic labeling, 1-dimensional electrophoresis and autoradiography. Further separation by 2-dimensional electrophoresis, however, revealed electrophoretically discernable variants of several groups of proteins at the higher Cu concentrations and the synthesis of a 60 kDa protein at (Cu2+) of 10(-9) M. In addition, there were differences in the stress response induced by heat-shock treatment in embryos cultured in seawater with different Cu concentrations; radiolabel was incorporated into a greater number of cellular proteins in embryos at lower (Cu2+) and the induced synthesis of stress proteins was greater. These data suggest that elevations in (Cu2+) impair the ability of the embryos to mount the stress response upon exposure to elevated temperatures and that Cu may alter critical developmental pathways by inhibiting the synthesis of regulatory proteins. Such effects on gene expression can result in manifestations that have been widely attributed to Cu toxicity, including developmental abnormalities and increased sensitivity to environmental extremes. We suggest that the particular sensitivity of embryonic systems upon exposure to multiple stressors may be a consequence of these mechanisms.

The importance of thyroid hormones (TH) in the normal development of muscles has been repeatedly postulated. The effects of physiological TH doses on ornithine decarboxylase (ODC) and protein synthesis in muscle cells have been studied using cell cultures prepared from 11-day-old chick embryos. Triiodothyronine nuclear receptors in primary muscle cell culture were characterized on the basis of the specific binding analysis as a single receptor class with the equilibrium dissociation constant Kd = 1.2 +/- 0.4 x 10(-10) mol/l and binding capacity Bmax = 0.21 +/- 0.09 fmol/micrograms DNA. While the physiological amounts of both triiodothyronine (T3) and thyroxine (T4) stimulated ODC activity after 2 hr of treatment, only T3 had the same stimulatory effect after 4 hr of treatment. Twenty-four hour exposure of muscle cell culture to TH did not change ODC activity. The incorporation of [3H]leucine into proteins was elevated only after 120 hr incubation in the presence of T4. Application of T4 caused also an increase in the protein content after 24 hr.

Lindane (gamma-hexachlorocyclohexane) influence on the in vitro intestinal transport of D-galactose and L-leucine has been studied in isolated chicken enterocytes. Animals were injected i.p. with 30 mg/kg b.w. of the pesticide over 7 days. Total uptake of D-galactose and L-leucine was significantly decreased by lindane action. There was no alteration in the non-mediated component, but the mediated transport was markedly inhibited in both cases. Furthermore, the exit of D-galactose across the basolateral membrane, as well as (Na(+)-K+)-ATPase activity, was significantly decreased in pesticide-treated chickens.

The effects of potassium (K+), noradrenaline (NA), serotonin (5-HR), histamine (Hi) and prostaglandin F2 alpha (PGF2 alpha) were studied on isolated pudendal arteries from non-lactating goats. K+, NA, 5-HT, Hi and PGF2 alpha had concentration-dependent contractile effects on the arteries. The developed tensions were, in order of potencies, 5-HT > NA > PGF2 alpha > Hi > K+. NA induced a significantly higher maximal contractile force than K+, 5-HT, PGF2 alpha and Hi. Pretreatment with cocaine was without significant effect on the contractile response to NA. The contractile response to Hi was totally eliminated by mepyramine. Ca2+ had a concentration-dependent contractile effect on arteries depolarized by 125 mM K+. The results indicate that NA, 5-HT and PGF2 alpha may play essential roles in the regulation of goat mammary blood flow. The response to K+ is highly dependent on extracellular Ca2+. The contractile response to histamine may be mediated via H1-receptors. The in vitro method used is well suited to study the vascular reactivity in different regions of the mammary vascular bed.

Lactation in seals is characterized by a rapid and enormous lipid transfer from mother to pups within a milk rich in lipids. Since grey seals do not feed during lactation, all milk constituents are solely derived from body stores. Monitoring levels of fat-soluble vitamins as well as PCBs in blubber and milk may give an insight into the mechanisms involved in their mobilization from blubber, transfer into milk and deposition in the blubber of pups. During lactation, total lipids in milk increased from 261 to 601 g/l. While the level of PCBs in milk per g lipid remained constant throughout lactation, vitamin E, as well as vitamin A and cholesterol, showed a marked decrease during lactation when expressed as quantity per unit lipid. An incomplete transfer of all components from maternal blubber to milk was observed, except for vitamin E. The milk of pregnant females had vitamin E levels per unit which were three times higher than that in blubber, indicating a mobilization of vitamin E from the liver. During the later stages of lactation, there were no differences between the levels of vitamins A and E per unit lipid in the milk and the blubber of suckling pups. The close correlation of PCBs with total milk lipids and the drastic decrease in all other monitored fat-soluble components in seal milk with the progress of lactation point to different mechanisms of mobilization and transport for triglycerides and PCBs compared to fat-soluble vitamins and cholesterol.

Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. Its presence in coffee, tea, soda beverages, chocolate and many prescription and over-the-counter drugs makes it a commonly consumed stimulant. Coffee and/or caffeine consumption has been linked to many human diseases in epidemiologic studies. Causal relationships have been difficult to substantiate. Initial investigations, showing an association between coffee and coronary heart disease, suffer from confounding variables and have been difficult to replicate. Recent studies, showing a significant effect over long follow-up periods and with high coffee intake, have again raised the question of a role for coffee and/or caffeine consumption in the pathogenesis of atherosclerotic heart disease. Contrary to common belief, the published literature provides little evidence that coffee and/or caffeine in typical dosages increases the risk of infarction, sudden death or arrhythmia.

BHA (2(3)-tert-butyl-4-hydroxyanisole) produced inhibition of both culture growth and oxygen consumption, NAD(P) reduction and cytochrome b oxidation, on intact epimastigotes of Trypanosoma cruzi. BHA inhibited respiration and reduced NAD(P) in intact T. cruzi trypomastigotes. Oxidative phosphorylation of in situ mitochondria of epimastigotes was inhibited by BHA and this effect was liberated by the addition of ascorbate+TMPD. The incorporation of rhodamine-123 to mitochondria of living epimastigotes was diminished by BHA. These results suggest that the basis of the trypanocidal effects of BHA could be due to the blockage of the mitochondrial electron transport chain on the segment previous to cytochrome c. We postulate that the mechanism of action of BHA could be by mimicking coenzyme-Q (ubiquinone).