ABSTRACT
The effects of fusaric acid on hepatic energy metabolism were measured. Three experimental systems were employed: (a) Intact rat liver mitochondria; (b) freeze-thawing disrupted mitochondria; and (c) the isolated perfused rat liver. Fusaric acid affects mitochondrial energy metabolism by at least three modes of action: (1) Inhibition of succinate-dehydrogenase (in the 10(-3)-10(-2) M range); (2) inhibition of oxidative phosphorylation (in the 10(-5)-10(-4) M range); and (3) inhibition of alpha-ketoglutarate-dehydrogenase (in the 10(-5)-10(-4) M range). The inhibition of oxidative phosphorylation seems to be the result of a direct action on the ATP-synthase/ATPase without significant inhibition of the ATP/ADP exchange. In the isolated perfused rat liver, fusaric acid inhibits oxygen uptake and gluconeogenesis from pyruvate, the latter being strictly dependent on intramitochondrially generated ATP. The effects of fusaric acid on rat liver mitochondria are similar to those reported previously for maize root mitochondria. However, except for the action on succinate-dehydrogenase, rat liver mitochondria are approximately two orders of magnitude more sensitive than maize root mitochondria.
Subject(s)
Fusaric Acid/pharmacology , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Energy Metabolism , Gluconeogenesis/drug effects , Liver/drug effects , Liver/metabolism , Oxygen/metabolism , Oxygen/pharmacokinetics , Oxygen Consumption/drug effects , Perfusion , Plant Roots/drug effects , Plant Roots/metabolism , Rats , Rats, Wistar , Zea mays/drug effects , Zea mays/metabolismABSTRACT
REM sleep deprivation (REMSD) results in behavioral changes such as the appearance of affective aggression induced by apomorphine (APO) and other dopaminergic agents. REMSD modifies dopamine-mediated behavior as well as the adrenergic receptor sensitivity. This paper evaluates the interaction between these two neurotransmission systems through changes in APO-, DL-DOPA- and fusaric acid (FA)-induced aggressive behavior in REMSD rats pretreated with phentolamine, propranolol, metaraminol, prazosin, clonidine, yohimbine, isoproterenol, butoxamine and maprotiline. Only isoproterenol reduced FA-induced aggressiveness. No specific changes in aggressiveness were noticed with other treatments and not even inhibitors of norepinephrine transmission induced aggressive behavior. It is concluded that norepinephrine had a slight inhibitory action on aggressiveness elicited by dopaminomimetic agents in REMSD rats. Beta-adrenoceptors could be responsible for this effect since only beta-selective drugs reduced aggression. As REMSD reduces beta-adrenoceptor sensitivity, only minor changes in aggressiveness could be observed. It was noted that the three drugs used to induce aggressive behavior elicited different patterns of aggression.
Subject(s)
Aggression/drug effects , Apomorphine/pharmacology , Brain/drug effects , Dihydroxyphenylalanine/pharmacology , Fusaric Acid/pharmacology , Receptors, Adrenergic/drug effects , Sleep Deprivation/physiology , Sleep, REM/drug effects , Sympatholytics/pharmacology , Sympathomimetics/pharmacology , Aggression/physiology , Animals , Brain/physiology , Isoproterenol/pharmacology , Norepinephrine/physiology , Phentolamine/pharmacology , Propranolol/pharmacology , Rats , Sleep, REM/physiologyABSTRACT
The role of dopamine as a neurotransmitter in the retina of different species has been clearly established; however, there is still some controversy as to whether noradrenaline (NA) is present as a neurotransmitter in this tissue. In this study, we show that, under controlled conditions, NA is present in the retina of goldfish at a concentration of 0.15 +/- 0.03 ng/mg protein and its biosynthetic enzyme, dopamine beta-hydroxylase shows an activity of 2.5 +/- 0.2 pmol NA/hr/mg protein. The amount of NA increases to 1.88 +/- 0.24 ng/mg protein in light adapted animals and decreases to undetectable levels in dark adapted ones. By contrast, dopamine-beta-hydroxylase levels are not affected by changes in light conditions. This finding provides further evidence in favor of a neurotransmitter role for NA in vertebrate retina.
Subject(s)
Neurotransmitter Agents/physiology , Norepinephrine/physiology , Retina/physiology , Adaptation, Physiological , Animals , Darkness , Dopamine/metabolism , Dopamine beta-Hydroxylase/metabolism , Fusaric Acid/pharmacology , Light , Methyltyrosines/pharmacology , Norepinephrine/metabolism , Periodicity , Retina/enzymology , Retina/metabolism , Time Factors , alpha-MethyltyrosineABSTRACT
LHRH (100 micrograms/kg. SC) impairs the acquisition of two-way avoidance conditioning. This is partially potentiated by pretreatment with alpha-methyltyrosine (alpha-MT; 250 mg/kg IP) or fusaric acid (10 mg/kg IP). L-DOPA (100 mg/kg IP) administered 5 h after alpha-MT partially reversed its effects. The possible roles of brain catecholamines on the behavioral effects of LHRH are analysed. Other tentative mechanisms of action are also discussed.