Apomorphine: modification of its hyperthermic effect in rabbits by p-chlorophenylalanine

The hyperthermic response of rabbits to apomorphine, a dopaminergic agonist, is abolished by prior treatment with p-chlorophenylalanine. If such 5-hydroxytryptamine (5-HT)-depleted animals are administered a peripherally acting decarboxylase inhibitor plus 5-hydroxytryptophan, central stores of 5-HT are regenerated and the hyperthermic response to apomorphine is restored in part. The effects of apomorphine in rabbits with elevated concentrations of 5-HT are not different from those in control animals. The behavioral effects of apomnorphine appear to be constant in all groups of animals tested. It is suggested that the hyperthermic effects of apomorphine in rabbits require the presence of 5-HT.     

Origin of 5-hydroxyindoleacetic acid in the spinl fluid

5-Hydroxyindoleacetic acid applied intracisternally in cats does not appear in spinal fluid. Changes of 5-hydroxyindoleacetic acid concentration in the spinal cord are clearly reflected in the perfusate of the spinal subarachnoid space. Thus, 5-hydroxyindoleacetic acid in the spinal fluid originates from the spinal cord and reflects metabolic changes of 5-hydroxytryptamine in the spinal tissue, but not those in the brain.     

Lysergic acid diethylamide: role in conversion of plasma tryptophan to brain serotonin (5-hydroxytryptamine)

Injections of D-lysergic acid diethylamide decrease the turnover rate of 5-hydroxytryptamine of rat brain, as measured from the conversion of (14)C-tryptophan into (14)C-5-hydroxytryptamine. The 2-bromolysergic acid diethylamide given in doses fivefold greater than those of lysergic acid diethylamide fails to change the rate of (14)C-tryptophan conversion into (14)C-5-hydroxytryptamine. The effect of D-lysergic acid diethylamide is discussed with regard to its action on brain serotonergic neurons and its psychotomimetic effects.     

哺乳仔猪外周血5-羟色胺的合成与代谢研究

[目的]探讨哺乳仔猪外周血5-羟色胺的合成与代谢随日龄变化的规律。[方法]选用15只0、5和15日龄的英系大白猪为试验动物,采用反相高效液相色谱——紫外检测法对其外周血血清中L-Trp、5-HT和5-HIAA的含量进行测定。[结果]仔猪初生时L-Trp的含量为（16.92±1.74）μmol/L,5日龄时为（59.94±10.88）μmol/L,15日龄时为（70.42±6.48）μmol/L;仔猪初生时5-HT的含量为（12.85±1.79）μmol/L,5日龄时为（4.81±2.05）μmol/L,15日龄时为（5.49±1.09）μmol/L;代谢产物5-HIAA在各日龄仔猪血清中均未检出。[结论]随日龄增加,哺乳仔猪外周血L-Trp的含量显著增加（P〈0.05）,而5-HT的含量与L-Trp-5-HT通路转化率在初生时最高（P〈0.05）,此后趋于稳定（P〉0.05）。     

Compulsive sexual activity induced by p-chlorophenylalanine in normal and pinealectomized male rats

p-Chlorophenylalanine depletes brain serotonin and induces longlasting sexual excitation in male rats. The effect of p-chlorophenylalanine is potentiated by pargyline. Administration of 5-hydroxytryptophan to rats treated with p-chlorophenylalanine plus pargyline blocks the sexual excitation. p-Chlorophenylalanine also elicits sexual excitation in pinealectomized rats; this effect is not mediated by the lack of indole hormones in the pineal but may be the consequence of depletion of 5-hydroxytryptophan in the brain and the resulting imbalance between 5-hydroxytryptophan and catecholamine activity in the central nervous system.     

Brain tryptophan hydroxylation: dependence on arterial oxygen tension

The accumulation of cerebral 5-hydroxytryptophan after decarboxylase inhibition was decreased in rats maintained at arterial O(2) tensions below 60 mm-Hg. In contrast, brain lactate was stable above 40 mm-Hg and brain adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate were unchanged above 30 mm-Hg. There was a linear correlation of brain 5-hydroxytryptophan accumulation to cerebral venous O(2) tension. Cerebral tryptophan hydroxylase appears to have a poor affinity for oxygen and to be affected by slight hypoxia. The resultant decreases in monoamine neurotransmitter metabolism may explain the behavioral changes of mild oxygen deprivation.     

Morphine tolerance, physical dependence, and synthesis of brain 5-hydroxytryptamine

Tolerance and physical dependence development to morphine in mice can be prevented by concomitant administration of cycloheximide. The fact that the rate of synthesis of brain 5-hydroxytryptamine (5HT) increases with tolerance to morphine suggests that the protein involved may be associated with 5HT synthesis. Inhibition of this synthesis with p-chlorophenylalanine markedly decreases tolerance and physical dependence development to morphine.     

5-Hydroxyindoleacetic acid in the lumbar fluid: a specific indicator of spinal cord injury

In cats, 19 days after the lower thoracic cord was injllred, the concentrations of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid in the lumbosacral cord and that of 5-hydroxyindoleacetic acid in the lumbar fluid decreased. At the same time the concentrations of these substances in the cord above the lesion and that of 5-hydroxyindoleacetic acid in the cisternal fluid was not significantly altered. Since high concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid are present in the human lumbosacral cord, it appears that the concentration of 5-hydroxyincdoleacetic acid in the lumbar fluid of animals and man reflects the biochemical changes of 5-hydroxytryptamine in the spinal cord.     

Alterations in 5-HT1B receptor function by p11 in depression-like states

The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT1B receptor agonists and reduced behavioral reactions to an antidepressant.     

Depression of norepinephrine and 5-hydroxytryptamine in the brain by benzoquinolizine derivatives

The effects of two benzoquinolizine derivatives on the 5-hydroxytryptamine and norepinephrine content of the brain of mice, and some pharmacological actions, are described. Certain central effects (such as sedation and narcosis potentiation) of benzoquinolizine derivatives and possibly of Rauwolfia alkaloids may be due to changes of norepinephrine metabolism rather than to changes of 5-hydroxytryptamine metabolism in the brain.     

Inhibition of gastric acid secretion in rats by intracerebral injection of corticotropin-releasing factor

Intracisternal injection of ovine corticotropin-releasing factor (CRF) into the pylorus-ligated rat or the rat with gastric fistula resulted in a dose-dependent inhibition of gastric secretion stimulated with pentagastrin or thyrotropin-releasing hormone. When injected into the lateral hypothalamus--but not when injected into the cerebral cortex--CRF suppressed pentagastrin-stimulated acid secretion. The inhibitory effect of CRF was blocked by vagotomy and adrenalectomy but not by hypophysectomy or naloxone treatment. These results indicate that CRF acts within the brain to inhibit gastric acid secretion through vagal and adrenal mechanisms and not through hypophysiotropic effects.     

Insect salivary glands: stimulation of fluid secretion by 5-hydroxytryptamine and adenosine-3',5'-monophosphate

Low concentrations (10(-9)M) of 5-hydroxytryptamine increase the rate of fluid secretion by isolated salivary glands of adult Calliphora. 5-Hydroxytry ptamine is present in Calliphora brain. Adenosine-3',5'-monophosphate (cyclic AMP) also stimulates fluid secretion and may be involved in the mode of action of 5-hydroxytryptamine.     

Neurosteroids: cytochrome P-450scc in rat brain

The steroid hormones corticosterone and testosterone are supplied to the central nervous system by endocrine glands, the adrenals and gonads. In contrast, the 3 beta-hydroxy-delta 5-derivatives of cholesterol, pregnenolone and dehydroepiandrosterone, accumulate in the rat brain through mechanisms independent of peripheral sources. Immunohistochemical studies have been performed with specific antibodies to bovine adrenal cytochrome P-450scc, which is involved in cholesterol side-chain cleavage and pregnenolone formation. The enzyme was localized in the white matter throughout the brain. Scarce clusters of cell bodies were also stained in the entorhinal and cingulate cortex and in the olfactory bulb. These observations strongly support the existence of "neurosteroids," which have been posited on the basis of biochemical, physiological, and behavioral studies.     

Diazepam-binding inhibitor: a neuropeptide located in selected neuronal populations of rat brain

An endogenous polypeptide of rat brain has been identified that is capable of displacing 1,4-benzodiazepines and the esters of the 3-carboxylic acid derivatives of beta-carbolines from their specific synaptic binding sites. This polypeptide was termed diazepam-binding inhibitor (DBI). Previous studies have shown that DBI injected intraventricularly in rodents elicits "proconflict" responses and antagonizes the "anticonflict" action of benzodiazepines. An antiserum to this peptide, directed toward an immunodeterminant near its amino terminus, makes it possible to detect, measure, and study the neuronal location of this peptide in rat brain. In the rat cerebral cortex, DBI immunoreactivity is located in neurons that are not GABAergic (GABA, gamma-aminobutyric acid); in the cerebellum and hippocampus, however, it might be present also in GABAergic neurons.     

Duchenne muscular dystrophy: functional ischemia reproduces its characteristic lesions

The highly characteristic early and midstage histological lesions of Duchenne dystrophy were reproduced experimentally in the rat by the combination of a vascular abnormality, aortic ligation, which does not affect the structure of the intramuscular blood vessels, and the humoral vasoactive substance 5-hydroxytryptamine. Neither ligation nor injection of 5-hydroxytryptamine alone causes changes in the muscle fibers. This result establishes the possibility of a similar combined mechanism for a nonstructural ischemia pathogenesis in Duchenne dystrophy. The proposed pathogenesis is contrary to the generally held idea that the cause is an intrinsic abnormality of muscle fiber metabolism.     

1-delta9-tetrahydrocannabinol: neurochemical and behavioral effects in the mouse

Administration of pure 1-delta(9)-tetrahydrocannabinol to mice had the following dose-dependent nzeurochemical and behavioral effects: a slight but significant increase in concentrations of 5-hydroxytryptamine in whole brain; a decrease in concentration of norepinephrine in brain after administration of low doses and an increase after high doses; diminished spontaneous activity, mloderate hypothermnia, hypersetisitivity to tactile and auditory stimiuli, and ataxia after low doses; and sedation, pronounced hypothermia, and markedly diminished spon taneous activity and reactivity after high doses. The duration of the effects on body temperature and spontaneous activity correlated generally with the changes in brain amines. The characteristic changes in brain amines do not correspond exactly to those observed with other psychotropic drugs.     

Ethanol oxidation: effect on the redox state of brain in mouse

Administration of a single large dose of ethanol to mice results in increases, for concentrations in the brain, of ratios of lactate to pyruvate, of aglycerophosphate to dihydroxyacetone phosphate, of malate to oxaloacetate, and of glutamate to the product of alpha-ketoglutarate and ammonium ion. These changes are noticed as early as 5 minutes after the single dose is given. Ethanol administration for 30 days also produces these changes in metabolite concentrations in the brain. However, in contrast to the single alcohol dose, long-term alcohol administration results in a marked decrease in the concentration of adenosine triphosphate in brain and increases in those of adenosine diphosphate and adenosine monophosphate. Pyrazole, an inhibitor of alcohol dehydrogenase, prevents the effects of ethanol on the concentration of brain metabolites. These results may provide new insight into the biochemical and pharmacological effects of alcohol on brain metabolism and the importance of alcohol dehydrogenase activity in the brain.     

硝酸银诱导的大豆子叶中大豆Kunitz胰蛋白酶抑制剂的研究

采用二维电泳技术对硝酸银诱导的大豆子叶微粒体膜蛋白进行分离,利用四极杆-飞行时间串联质谱,对仅存在于诱导样品而不存在于对照样品中的蛋白质点进行氨基酸序列测定和分析,以期研究硝酸银处理对大豆子叶微粒体蛋白质的影响。结果显示:硝酸银可以诱导大豆Kunitz胰蛋白酶抑制剂(SKTI)的产生,在诱导处理的子叶中大量存在其成熟形式,也存在其5 kDa小亚基,小亚基含有“GIGTIISSPER”和“FIAEGNPLR”氨基酸序列。该研究结果为SKTI的深入研究提供了实践依据,并为其分离纯化提供了简便途径,从而有利于对其更多性质的进一步研究。     

Neuromuscular transmitter substance in insect visceral muscle

Stimulation of the nerves innervating the proctodeum (hindgut) of the cockroach Periplaneta americana (L.) causes a slow-type, graded contraction of the longitudinal muscles. An unidentified substance, or substances, present in the foregut and hindgut, the specific activity of which is highest in the nerves innervating these organs, effects a similar contraction. This "gut-factor" is depleted from the hindgut after surgical section of the proctodeal nerves. None of Factors P(1) and P(2), 5-hydroxytryptamine, acetylcholine, adrenaline, noradrenaline, alpha-ami-nobutyric acid or glutamate duplicates the pharmacological behavior of this substance. The active factor is associated with subcellular particles that require centrifugal forces of approximately 1,000,000 g-min for sedimentation. The substance is inactivated in homogenates of gut tissue in the absence of suitable precautions. It is proposed that the "gut-factor" functions as an excitatory neuromuscular transmitter substance in insect visceral muscle.     

Blood-brain barrier: endogenous modulation by adrenal-cortical function

The blood-brain barrier restricts the passage of molecules from the blood to the brain. The permeability of the barrier to iodine-125-labeled bovine serum albumin was examined in rats that had undergone adrenalectomy, adrenal demedullation, and corticosterone replacement. Adrenalectomy, but not adrenal demedullation, increased the permeability of brain tissue to the isotopically labeled macromolecule; corticosterone replacement reversed this effect. These results indicate that the blood-brain barrier may be hormonally regulated; that is, the pituitary-adrenal axis may physiologically modulate the permeability of the brain microvasculature to macromolecules.