Whole blood and plasma histamine levels were measured in 27 non-medicated patients with common migraine. In nine cases blood was drawn 1-2 h after the onset of a migraine attack. The whole blood histamine levels of migraineurs and controls did not differ significantly. In contrast, histamine levels were significantly increased in plasma from patients both during and between migraine attacks, as compared with controls (p less than 0.001). Finally, plasma taken from migraine patients induced a significantly greater release of histamine from control whole blood than did plasma taken from control subjects (p less than 0.01).

Histamine and the guanosine 3',5'-cyclic monophosphate (cGMP)-inducing agent sodium nitroprusside both increased serotonin (5-HT) uptake and cGMP levels in isolated human platelets in vitro. Histaminergic stimulation was observed at concentrations ranging from 10 nM to 0.25 microM [mean effective concentration (EC50) = 0.1 microM histamine]. The inhibition produced by the H2-receptor antagonists tiotidine, metiamide, and cimetidine was 10-10(5) times more potent on histamine receptors regulating 5-HT uptake and cGMP generation in human platelets than on the histaminergic receptors H1, HIC, H2, and H3 in other tissues. The in vitro histamine-induced 5-HT uptake was prevented by preincubation of isolated human platelets in the presence of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine or the cGMP-lowering agent LY-83583. Histamine was ineffective in stimulating cAMP generation in human platelets and did not interact with effector sites known to downregulate 5-HT uptake, including imipramine, gamma-aminobutyric acid A, peripheral type benzodiazepine-binding sites, and V1a vasopressin receptors inducing human platelet shape change and aggregation. These atypical human platelet histaminergic receptors differ from the previously classified histamine receptors by their apparent high affinity to histamine H2-receptor antagonists and their apparent link with the soluble, nitric oxide-dependent guanylate cyclase. These findings suggest that human platelets express a new subtype H2h of histamine receptors.

The serotonin metabolism was extensively studied in 22 couples of autistic children and age- and sex-matched controls. Histamine, calcium, and uric acid were also measured in urine and whole blood or plasma. Autistics and controls did not differ in histamine, and only minor changes were noticed in calcium content. According to previous reports, serotonin levels were often, but not always, evelated in the blood of autistic children. Based on data including urinary serotonin and 5-hydroxyindoleacetic acid, platelet serotonin uptake and efflux, platelet monoamine oxidase and glutathione perixodase activities, and uric acid and plasma tryptophan, the origin(s) of such hyperserotonemia in autism appear(s) to be of metabolic origin, i.e., a decreased catabolism and/or an increased biosynthesis of serotonin.

A modified highly sensitive and specific radioenzymatic assay for the simultaneous determination of histamine (HA) and N alpha-methylhistamine (N alpha-MH) in tissues and body fluids is described. In the presence of the enzyme histamine-N-methyltransferase and of the methyl donor [3H]-S-adenosylmethionine, the transmethylation process was about seven times more effective for HA than for N alpha-MH. In the same conditions only very low amounts of N alpha, N alpha-dimethylhistamine (N alpha, N alpha-DMH) were converted into its 1-methylated derivative. The high degree of specificity attained by this method is due to the rapid quantitative extraction of the biological fluids, to the partially purified enzyme preparation and to the thin-layer chromatography system used which allows an excellent separation of the 3H-1-methyl products of HA, N alpha-MH and N alpha, N alpha-DMH. This method is highly sensitive for the assay of HA and N alpha-MH (detection limit 10 and 50 picograms, respectively), but due to lack in sensitivity, it cannot be extended to the measurement of N alpha, N alpha-DMH. The HA content of 20-30 samples can be determined in duplicate by one person in a working day. The concentrations of HA measured by this method in different biological samples (human whole blood, plasma, urine, gastric juice and skin biopsies) were in good agreement with the values reported in the literature. The presence of minute amounts of N alpha-MH in the human gastric juice was established by rigorous checking.