Distribution of an enzyme which acetylates α-melanocyte stimulating hormone in rat brain and pituitary gland and effects of arcuate nucleus lesions

This study describes the distribution of an α-melanocyte stimulating hormone (α-MSH) acetyltransferase (MAT) in rat brain and pituitary gland. Highest activities of MAT were found in the neurointermediate lobe of the pituitary gland with the anterior lobe containing slightly less. Within the brain, lowest MAT activities were measured in the hypothalamus, the region which contained the highest concentrations of α-MSH. Relatively high enzyme activities of MAT were measured in the hippocampus, cortex and cerebellum—regions with very low α-MSH concentrations. The fact that MAT activity levels did not parallel α-MSH concentrations indicates that MAT was not solely localized to α-MSH synthesizing neurons or endocrine cells. Furthermore, arcuate nucleus lesions which depleted brain α-MSH failed to deplete MAT activity. Although MAT was not solely localized to α-MSH synthesizing cells, it may have functional significance for α-MSH acetylation due to compartmentalization with α-MSH in α-MSH synthesizing endocrine cells and neurons. Alternatively a second regionally specific MAT may exist.     

On the separation of functions mediated by the AV3V region

Knife-cuts were used to separate the disruptive effects on fluid balance that are produced by electrolytic lesions of the anteroventral third ventricle (AV3V) region. It was observed that vertical cuts of the dorsal stalk of the subfornical organ (SFO) produced none of these effects. Horizontal cuts between the SFO and the anterior commissure produced neither of the acute effects of AV3V lesions (adipsia and diuretic weight loss) but they did mimic AV3V lesions in disrupting drinking responses to peripherally injected angiotensin and hypertonic saline. In contrast, horizontal cuts between the anterior commissure and the organum vasculosum of the lamina terminalis (OVLT) did not reduce drinking responses to angiotensin but they did cause a large weight loss during the 24 hours following surgery. It is suggested that these ventral cuts severed neural connections between the medial septum and the ventral medial preoptic area in producing the large weight loss. Together with findings from other experiments, these findings support the hypothesis that distinct neural elements mediate the various functions that are disrupted by lesions of the AV3V region.     

Synaptology of neurosecretory cells in the nucleus paraventricularis of the domestic fowl

Summary Processes of magnocellular neurosecretory cells (MNCs) are easily identifiable on the basis of their content in neurosecretory granules in the neuropil of the rostral division of the paraventricular nucleus (PVN) of the domestic fowl. In specimens sacrificed during the winter the synaptic organization of the neuropil and the pattern of synapses ending on neurosecretory processes were studied at the ultrastructural level. Synapses in the rostral part of the PVN neuropil may be divided into three main categories on the basis of their morphology and their content of clear and dense-core synaptic vesicles. These different types of terminals can be attributed to aminergic, peptidergic or other types of synapses. The percent distribution of synapses within these categories differs when all synapses observed in the neuropil or only those ending on MNC processes are compared. Present ultrastructural data obtained in birds support two physiological hypotheses already suggested for mammals, i.e., the probable existence of a recurrent pathway to MNCs via an interneuron, and the importance of aminergic and peptidergic input in regulating the electrical activity of MNCs.This work was partly supported by a CNR grant (n. 81.00377.04)     

Free postsynaptic sites in the lateral geniculate nucleus of adult cats following chronic decortication

Summary Following chronic decortication, free postsynaptic sites were found in the lateral geniculate nucleus of adult cat. Quantitative electron-microscopic analysis of the free postsynaptic sites revealed that they were not identical with the original, vacant postsynaptic sites, but were newly assembled formations. The ability of both relay cells and local interneurons of the adult lateral geniculate nucleus to assemble and/or maintain postsynaptic sites indicates that these nerve cells may be involved in the formation of new synapses.     

Effect of chlorinated naphthalenes and terphenyls on the activities of drug metabolizing enzymes in rat liver

γ-Aminobutyric acid-α-ketoglutarate transaminase from pig brain is irreversibly inactivated by 4-amino-5-halopentanoic acids. Protection from inactivation by the natural substrates, the pH dependence of inactivation and the incorporation of 1.7 moles of radioactive inhibitor per mole of enzyme from (S)-[U-¹⁴C]-4-amino-5-chloropentanoic acid suggest a covalent adduct at the active site of the enzyme. A mechanism-based inactivation is proposed.     

Neuroanatomical Distribution and Variations across the Reproductive Cycle of Aromatase Activity and Aromatase-Immunoreactive Cells in the Pied Flycatcher (Ficedula hypoleuca)

The anatomical distribution and seasonal variations in aromatase activity and in the number of aromatase-immunoreactive cells were studied in the brain of free-living male pied flycatchers (Ficedula hypoleuca). A high aromatase activity was detected in the telencephalon and diencephalon but low to negligible levels were present in the optic lobes, cerebellum, and brain stem. In the diencephalon, most aromatase-immunoreactive cells were confined to three nuclei implicated in the control of reproductive behaviors: the medial preoptic nucleus, the nucleus of the stria terminalis, and the ventromedial nucleus of the hypothalamus. In the telencephalon, the immunopositive cells were clustered in the medial part of the neostriatum and in the hippocampus as previously described in another songbird species, the zebra finch. No immunoreactive cells could be observed in the song control nuclei. A marked drop in aromatase activity was detected in the anterior and posterior diencephalon in the early summer when the behavior of the birds had switched from defending a territory to helping the female in feeding the nestlings. This enzymatic change is presumably controlled by the drop in plasma testosterone levels observed at that stage of the reproductive cycle. No change in enzyme activity, however, was seen at that time in other brain areas. The number of aromatase-immunoreactive cells also decreased at that time in the caudal part of the medial preoptic nucleus but not in the ventromedial nucleus of the hypothalamus (an increase was even observed), suggesting that differential mechanisms control the enzyme concentration and enzyme activity in the hypothalamus. Taken together, these data suggest that changes in diencephalic aromatase activity contribute to the control of seasonal variations in reproductive behavior of male pied flycatchers but the role of the telencephalic aromatase in the control of behavior remains unclear at present.     

A Giant Ubiquitin-conjugating Enzyme Related to IAP Apoptosis Inhibitors

Ubiquitin-conjugating enzymes (UBC) catalyze the covalent attachment of ubiquitin to target proteins and are distinguished by the presence of a UBC domain required for catalysis. Previously identified members of this enzyme family are small proteins and function primarily in selective proteolysis pathways. Here we describe BRUCE (BIR repeat containing ubiquitin-conjugating enzyme), a giant (528-kD) ubiquitin-conjugating enzyme from mice. BRUCE is membrane associated and localizes to the Golgi compartment and the vesicular system. Remarkably, in addition to being an active ubiquitin-conjugating enzyme, BRUCE bears a baculovirus inhibitor of apoptosis repeat (BIR) motif, which to this date has been exclusively found in apoptosis inhibitors of the IAP-related protein family. The BIR motifs of IAP proteins are indispensable for their anti–cell death activity and are thought to function through protein–protein interaction. This suggests that BRUCE may combine properties of IAP-like proteins and ubiquitin-conjugating enzymes and indicates that the family of IAP-like proteins is structurally and functionally more diverse than previously expected.     

Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat

The effects of microinfusingl-glutamate, serotonin (5-HT), (±)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH DPAT; a 5-HT_1A agonist), and muscimol (a GABA_A agonist) into the dorsal raphe nucleus on the extracellular levels of 5-HT, dopamine (DA) and their metabolites in the nucleus accumbens were studied in unanesthetized, freely moving, adult male Wistar rats, using the technique of microdialysis coupled with small-bore HPLC. Administration of 0.75 gl-glutamate produced a 25–50% increase (P<0.05) in the extracellular levels of both 5-HT and DA. On the other hand, infusion of 8-OH DPAT and, to a lesser extent, 5-HT produced a significant (P<0.05) decrease in the extracellular levels of both 5-HT and DA. Muscimol (0.25 or 0.50 g) had little effect on the extracellular concentrations of 5-HT or DA following its administration. In general, the extracellular levels of the major metabolites of 5-HT and DA in the nucleus accumbens were not altered by microinfusion of any of the agents. The data indicate that (a) the 5-HT neurons projecting to the nucleus accumbens from the dorsal raphe nucleus can be activated by excitatory amino acid receptors and inhibited by stimulation of 5-HT_1A autoreceptors, and (b) the dorsal raphe nucleus 5-HT neuronal system may regulate the ventral tegmental area DA projection to the nucleus accumbens.Special issue dedicated to Dr. Morris H. Aprison     

甲状腺素和甲巯咪唑对大鼠视前区-下丘脑前部中及血清中单胺类递质的影响

反复皮下注射甲状腺素(T_4,1mg/100g·d,连续10d)和胃饲甲巯咪唑(10mg/100g·d,连续15d)后,用高效液相色谱加电化学检测器(HPLC-EGD)分析了大鼠视前区-下丘脑前部(PO/AH)中单胺神经递质的含量。发现经甲状腺素处理后,PO/AH区中多巴胺(DA)和高香草酸(HVA)含量显著增加,具有统计学意义(P<0.01),5-羟色胺(5-HT)和5-羟吲哚乙酸(5-HIAA)轻度上升,但无统计学意义(P>0.05),去甲肾上腺素(NE)无明显变化;经甲巯咪唑处理后的动物则出现NE含量显著下降(P<0.05),但DA、HVA、5-HT和5-HIAA各项变化不显著。本文还同步观察了外周血清中单胺介质含量的变化,结果表明其与中枢单胺介质含量变化基本上不同步。本文还讨论了甲状腺素和甲巯咪唑影响单胺介质含量和影响体温变化之间的关系。