Histamine Metabolites in Cerebrospinal Fluid of the Rhesus Monkey (Macaca mulatto): Cisternal‐Lumbar Concentration Gradients

Abstract

Similar to metabolites of other aminergic transmitters, histamine metabolites of brain, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), could have a concentration gradient between rostral and caudal sites of CSF. To test this hypothesis, cisternal and lumbar CSF samples were collected in pairs from eight monkeys (Macaca mulatta), and levels of t-MH and t-MIAA were measured by gas chromatography-mass spectrometry. pros-Methylimidazoleacetic acid (p-MIAA), an endogenous isomer of t-MIAA that is not a histamine metabolite, was also measured. Cisternal levels (in picomoles per milliliter, mean +/- SEM) of t-MH (9.9 +/- 1.4) and t-MIAA (40.8 +/- 7.6), but not of p-MIAA (9.7 +/- 1.2), exceeded those in lumbar CSF (t-MH, 1.8 +/- 0.3; t-MIAA, 6.8 +/- 0.9; p-MIAA, 8.6 +/- 0.6) in every monkey. The magnitudes of the mean cisternal-lumbar concentration gradients for t-MH (6.6 +/- 1.1) and t-MIAA (6.5 +/- 1.3) were indistinguishable. These gradients exceed those of metabolites of most other transmitters. There was no gradient for the levels of p-MIAA. The cisternal, but not lumbar, levels of t-MH and t-MIAA were correlated. There was no significant difference between the means of the metabolite concentration ratios (t-MIAA/t-MH) in cisternal (4.0 +/- 0.4) and lumbar (4.4 +/- 0.9) CSF. The steepness of these gradients suggests that levels of t-MH and t-MIAA in lumbar CSF might be useful probes of histaminergic metabolism in brain.

Rostral-caudal concentration gradients of histamine metabolites in human cerebrospinal fluid

“…The existence of concentration gradients for t-MH and t-MIAA in human CSF and the lack of a gradient for p-MIAA are similar to our findings in CSF from monkey [16]. With sequential removal of lumbar CSF, there was a linear rise in levels of t-MH and t-MIAA (Fig.…”

“…The lack of a concentration gradient for p-MIAA, which is not derived from histamine, further suggests that the gradients of t-MIAA and t-MH are derived from histaminergic metabolism and are not artefacts produced by organic acid transport out of the CSF. As summarized [16], the magnitude of the gradients for t-MH and t-MIAA between cisternal and lumbar CSF from monkey are in excess of those for NE, MHPG, and 5-HIAA, but are similar to those for HVA. As for HVA and 5-HIAA (e.g.…”

“…Therefore, the lower limit of detection for t-MH, approximately 0.66 pmol/ml, was assigned to this segment. There was a significant positive regression (r = 0.97; F= 29.4, p < 0.05) between the midpoint of each volume collected and the samples with measureable values of t-MH (3 samples from the subject studied for the gradient, ml 7-9, 10-12 and 18-20, and the mean of the values from the other controls, ml [14][15][16]. Use of the assigned value for t-MH raised the level of significance (F= 47.8, p < 0.01) but did not alter the correlation coefficient (Pearson) or slope (0.07 pmol/ml).…”

“…1) but below the slope they determined (1.45 pmol/ml 2, recalculated) for the female patient. Two questions not evaluated in the gradient study with monkey CSF [16] are the influence of diet on analyte levels and the potential contribution to lumbar CSF of metabolites derived from the spinal cord or plasma. Lumbar CSF metabolite levels showed little variation among the subjects.…”

“…Some evidence has been presented for a concentration gradient for t-MIAA [15]. t-MH did not show a rostral-caudal gradient [14,15]; however, concentration gradients for both t-MH and t-MIAA were observed in samples of cisternal and lumbar CSF removed from rhesus monkeys [16]. We report concentration gradients of both t-MH and t-MIAA in serial aliquots of lumbar CSF from a healthy male subject, pros-Methylimidazoleacetic acid (p-MIAA), an endogenousqsomer of t-MIAA, can be quantified in CSF along with t-MIAA [12]; it is not a histamine metabolite in brain [17].…”