Measurement of tele-methylhistamine and histamine in human cerebrospinal fluid,urine, and plasma

A gas chromatographic-mass spectrometric method described by us to measure tele-methylhistamine (t-MH) in brain was used to measure t-MH in human cerebrospinal fluid (CSF), urine and plasma. The presence of t-MH in these body fluids was rigorously established. No pros-methylhistamine could be detected, and it was used as internal standard to quantify t-MH in the fluids. The mean levels of t-MH were: urine, 943 pmol/mg creatinine; plasma, 12.3 pmol/ml; and CSF, 2.2 pmol/ml. Parallel measurements of histamine by a radioenzymatic method showed, respectively, 182 pmol/mg creatinine; 19.5 pmol/ml; and 388 pmol/ml. The levels of HA in CSF, much higher than those of its metabolite, t-MH, are high enough to stimulate HA receptors in the central nervous system.     

Kinetics of histamine and tele-methylhistamine elimination from rat plasma

Plasma levels of histamine (Hi) and tele-methylhistamine (MeHi) were measured by HPLC after intravenous bolus injection of Hi (45 g/kg) or MeHi (55 g/kg) in the rat. Increases in plasma Hi (from baseline 2.8±0.4 to about 50 ng/ml at 2 min after the injection) were accompanied by a significant increase in MeHi levels (baseline 1.2±0.3 ng/ml rising up to 11 ng/ml, 6 min after Hi application). After rapid intravenous injection, Hi and MeHi elimination from plasma could be fitted by a double exponential function with half lives in the and phases of about 20 sec and 4 min (Hi) or 1 min and 43 min (MeHi). The results suggest that measurement of plasma MeHi, as an indirect marker of Hi release, has an advantage over measuring Hi itself.     

Liver damage,voluntary alcohol intake and brain histamine

Liver dysfunction induced by portocaval anastomosis (PCA) in the rat is associated with a great reduction of hepatic alcohol and aldehyde dehydrogenase activities. Despite this, PCA rats voluntarily drank more alcohol than unoperated rats. When subjected to forced alcohol consumption, shunted rats maintained their exaggerated voluntary alcohol intake whereas unoperated rats developed aversion to alcohol. Hypothalamic levels of both histamine and histidine were very high in PCA rats. When these rats were chronically exposed to alcohol, there was a slight decrease in hypothalamic histidine concentration and consequently a lower histamine content. Chronic exposure to alcohol did not, however, influence hypothalamic tissue levels of histamine or histidine in unoperated rats. In both groups, chronic alcohol treatment exerted a stimulatory effect on hepatic alcohol metabolizing enzymes.     

Effects of tele-methylhistamine and metoprine on plasma levels of histamine and on its elimination from cat plasma

Inflammation Research -     

Effect of histidine on morphine-induced changes in brain histamine

Chronic morphine administration to rats resulted in a significant decrease in the hypothalamic and cerebro-cortical histamine concentrations. These low histamine values were restored to control levels whenl-histidine was administered daily along with morphine treatment. Chronic treatment withl-histidine prevented the midbrain and cerebro-cortical histamine depletion in morphine-withdrawn rats, whereas in the hypothalamus the histamine level remained significantly decreased.The present data suggests that histamine may play a role in morphine dependence and withdrawal.Part of this work was presented at the 19th annual meeting of the Canadian Federation of Biological Societies in Halifax, June 1976.This work was supported by the Ontario Metal Health Foundation Grant No. 379-71D.     

Effect of isolation stress on brain mast cells and brain histamine levels in rats

The effects of the chronic social stress of isolation on changes in brain mast cells (MC), the hypothalamic histamine content and the activity of the hypothalamic-pituitary adrenal (HPA) axis were investigated in rats.

Social stress of isolation markedly reduced the total number of brain mast cells, most significantly by 90% in the first day. The extent of MC degranulation, 36–67%, in stressed rats did not significantly differ from that in control animals, 45–58%. Isolation stress substantially, though not significantly, increased the hypothalamic histamine content. The serum corticosterone levels in isolated rats did not significantly differ from the control levels.

These results indicate that social stress of isolation considerably diminishes the number of brain MC and suggest that histamine which might be liberated from these cells does not significantly influence the HPA activity.

     

Increased plasma tele-methylhistamine levels in the rat: Effects on plasma and tissue histamine and its elimination

Inflammation Research -     

Effect of experimental hyper-and hypothyroidism on neonatal rat brain histamine levels

Conclusions These results suggest that thyroid hormones may regulate the levels of the mast cell HA pool in newborn rat brain. Since the largest number of mast cells is present in the brain at a time when brain maturation is highly influenced by thyroid hormones, brain mast cells may play an important role in brain development.     

Effect of amodiaquine on histamine level and histamine-methyltransferase activity in the rat brain

Amodiaquine, 10(-5) M, totally inhibited the activity of histamine-methyltransferase (HMT) in the rat brain. Both peripheral (60 mg/kg i.p.) and central (50 and 100 microgram i.vt.) administration of the drug substantially reduced the HMT activity. Amodiaquine given i.p. or i.vt., in various doses, did not change the endogenous histamine (HI) level in the rat brain at any time studied (1-24 h). Amodiaquine (60 or 120 mg/kg i.p.) administered together with an inhibitor of diamine oxidase, i.e. aminoguanidine (either peripherally or centrally) had no effect on the endogenous HI content. Possible involvement of mechanisms other than methylation or oxidation in regulation of the endogenous HI level in the rat brain is discussed.     

The manipulation of brain histamine concentrations failed to modify voluntary alcohol intake by rats

Inflammation Research -     

Effect of histamine methylation inhibitors on entry of14C-histamine into brain

Pretreatment of mice, rats and guinea pigs with inhibitors of histamine methylation, followed by sytemic injection of¹⁴C-histamine, results in a significant increase in brain¹⁴C-histamine relative to controls. It is suggested that the histamine methylating enzyme participates in the bloodbrain barrier to histamine.     

Effects of histamine on brain capillaries

Summary The effect of histamine administered via the common carotid artery on the transport processes of brain capillaries was investigated in rats. The fine structure of endothelial cells and the glial end-feet system was studied by electron microscopy and the serum albumin was visualized for light microscopy by the peroxidase-antiperoxidase (PAP) immunohistochemical reaction. Sixty microgram per milliliter histamine enhanced the penetration of serum albumin into the capillaries while the number of pinocytotic and coated vesicles significantly increased in the capillary endothelium. Oedematous swelling of the glial end-feet system was also observed. The stimulatory effect of histamine on the transcapillary transport could not be inhibited by a histamine H_1– receptor antagonist, mepyramine. By contrast, metiamide, a histamine H_2–-receptor antagonist prevented both ultrastructural changes and albumin penetration in the brain capillaries to occur.     

Effect of nitrendipine on histamine release from human basophil leukocytes

The effect of the new calcium antagonist nitrendipine on in vitro basophil activation was evaluated in 10 subjects. The histamine release induced by calcium ionophore A23187, f-met peptide and anti-IgE was inhibited, in a dose-dependent fashion, by nitrendipine in the concentration range of 1-100 microM. The activity of this calcium antagonist seems complex and related to an interference with calcium at multiple sites. At concentrations higher than 200 microM, nitrendipine causes histamine release from basophil leukocytes. This histamine secretion is likely to be due to a cytotoxic effect, since it is associated with an increase in LDH levels in the cell supernatant.     

Effect of disodium cromoglycate on antigen-evoked histamine release from human skin

The effect of disodium cromoglycate (DSCG) on antigen-evoked histamine release from IgE-sensitized human skin in vitro has been studied using breast skin from six donors. Concentrations of DSCG ranging from 10–200 μM did not produce any consistent effect on histamine release, the results ranging from moderate inhibition to moderate enhancement. With higher concentrations of DSCG (400–500 μM) enhancement of release occurred in nearly all experiments. Variation of antigen concentration did not modify the response to DSCG. These results do not support the possibility that DSCG may be effective in the treatment of immediate hypersensitivity reactions in human skin.     

Effect of histamine on tumor necrosis factor production by human monocytes

This study was aimed at evaluating the effect of histamine on tumor necrosis factor (TNF alpha) secretion by purified human blood monocytes. TNF alpha was measured by radioimmunoassay. Histamine caused a dose-dependent inhibition of lipopolysaccharide-induced TNF alpha production from human blood monocytes, averaging maximally 50% at 10(-5) M. Preincubation of mononuclear cells with an H2 antagonist (cimetidine), but not with an H1 antagonist (promethazine) prevented this inhibitory effect of histamine. In conclusion, histamine causes, in vitro, a depression of TNF alpha secretion by human monocytes through activation of H2 receptors.     

Effect of histamine on corticosteroid secretion of isolated human and rat adrenocortical cells

Inflammation Research -     

Semantic and visual memory after alcohol abuse

This study compared the relative performance of 40 patients (M age = 31.7) with a history of alcohol abuse on tasks of short-term semantic and visual memory. Performance on the visual memory tasks was impaired significantly relative to the semantic memory task in a within-subjects analysis of variance. Semantic memory was unimpaired. This result is consistent with previous results obtained on tests of intelligence despite the added requirement of encoding, storing, and retrieving data inherent in the memory tasks. This result provides support for the contention that visuospatial and visuomotor skills evince primary residual impairment secondary to the abuse of alcohol. The significance of this result, in light of previous research, is discussed.