The uptake and subcellular distribution of aromatic amines in the brain of the rat.
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To determine the importance of dopamine and noradrenaline as neurotransmitters during chemoreception in the cat carotid body we investigated the contents of both compounds as well as the activity of dopamine-beta-hydroxylase (DBH) under different arterial PO2 and PCO2 conditions. The superior cervical ganglion was used as a control organ. In the carotid body and the ganglion an inverse relationship exists between the catecholamine content and the DBH activity. The carotid body has a high catecholamine content with a low DBH activity whereas the superior cervical ganglion has a low catecholamine content and high DBH activity. Hypercapnia did not produce any significant change in the catecholamine content or in the DBH content of the carotid body. However, in comparison with hyperoxia, hypoxia produced a significant change (p less than 0.05) in the noradrenaline content without changing the DBH activity. The dopamine content under these conditions did not change significantly. The results may indicate that the high catecholamine content of the carotid body is the result of a high retention and/or low rate of degradation rather than of a high rate of synthesis.
Adenylate cyclase in homogenates of Drosophila melanogaster is heterogeneous with respect to its affinity toward MgATP and its subcellular distribution. Km values for MgATP range, under similar assay conditions, from approximately 10(-5) M to approximately 10(-3) M, depending on the body region and on the subcellular localization of the enzyme. The majority of the enzyme in whole-body preparations is particulate, but various body regions differ in the relative proportion of the soluble enzyme. The memory mutant rutabaga lacks up to 35% of the total particulate activity. Even ligands that stimulate directly the catalytic subunit are incapable of bringing the activity of the mutant's enzyme to normal levels. The defect is differentially pronounced in various body parts and is associated with an altered responsiveness of the enzyme to Mg2+, to Ca2+, and to forskolin. It is suggested that rutabaga is lesioned in a subpopulation, or a functional state, of adenylate cyclase, which may play a role in memory formation.
Intracerebroventricular injections of angiotensin II caused 108, 62, and 54% increases in monoamine oxidase A activities in rat hippocampus, hypothalamus, and striatum, respectively. These activatory effects were abolished by simultaneous injections of eledoisin. No significant changes of monoamine oxidase B activities were found under the same experimental conditions. Neither angiotensin II nor elodoisin changed substrate/inhibitor affinities of both isoenzymes. These data indicate that angiotensin II and tachykinin transmitter systems may exert opposite, long-term regulatory effects on monoaminergic neurons in rat brain.
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1 To elucidate the mechanism by which amphetamine produces a functional inhibition of dopamine beta-hydroxylase (DBH), the actions of amphetamine on amine uptake and beta-hydroxylation were examined in isolated adrenal storage vesicles and in whole brain synaptosomes of the rat. 2 Amphetamine produces a competitive inhibition of catecholamine incorporation into adrenal vesicles with a Ki of 279 muM; this action of the drug accounted for slightly less than half of the total inhibition of beta-hydroxylation in the vesicles, indicating that the interference by amphetamine of access of substrate to the enzyme compartment plays an important role in functional inhibition of DBH. The remainder of the effect in vesicles probably represents direct inhibition of the enzyme. 3 In synaptosomes, similar actions on uptake of substrate and on functional enzyme activity were noted, indicating that amphetamine-induced inhibition of the neuronal amine pump can also affect DBH activity if the substrate is supplied exogenously. 4 In addition to the effects of amphetamine in vitro, chronic administration of amphetamine to rats produced an increase in total activity of adrenal DBH. 5 The net effect of amphetamine on DBH activity thus represents the summation of direct inhibition of the enzyme, indirect inhibition via reduced access of substrate and enhancement of activity via trans-synaptic induction.
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