Normal cerebrospinal fluid histamine and tele-methylhistamine levels in hypersomnia conditions.

STUDY OBJECTIVES: To determine the activity of cerebral histaminergic system evaluated by CSF levels of histamine (HA) and tele-methylhistamine (t-MHA), its major metabolite, and their relationships with hypocretin-1 levels in a large population of patients with hypersomnia and neurological conditions. DESIGN: sensitive liquid chromatographic-electrospray/tandem mass spectrometric assay was developed for the simultaneous quantification of CSF HA and t-MHA. SETTING: ata were collected and CSF hypocretin-1 levels were measured using radioimmunoassay at the Sleep Disorders Center, Montpellier, France. CSF HA and t-MHA were measured in Bioprojet-Biotech, France PARTICIPANTS: One hundred fourteen unrelated patients with a suspicion of central hypersomnia underwent one night of polysomnography followed by the multiple sleep latency test. Sleep disorders were diagnosed clinically and using sleep studies: narcolepsy-cataplexy NC (n = 56), narcolepsy without cataplexy NwC (n = 27), idiopathic hypersomnia IH (n = 11), secondary narcolepsy (n = 3), and unspecified hypersomnia Uns EDS (n = 17). Fifty neurological patients without daytime sleepiness were included as controls. MEASUREMENTS AND RESULTS: No between-hypersomnia group differences were found for CSF HA levels (median 708.62 pM extreme range [55.92-3335.50] in NC; 781.34 [174.08-4391.50] in NwC; 489.42 [177.45-906.70] in IH, and 1155.40 [134.80-2736.59] in Uns EDS) or for t-MHA levels. No association was found between CSF HA, t-MHA, or HA + t-MHA, sleepiness, treatment intake, and frequency of cataplexy. A slight negative correlation was found between age and HA levels. Further adjustment for the age revealed no significant HA levels difference between hypersomnia patients and controls. CONCLUSION: CSF histamine and tele-methylhistamine did not significantly differ between patients with narcolepsy-cataplexy and other etiologies of non-hypocretin-1 deficient central hypersomnias; these measurements, therefore, are not useful in assessing the etiology or severity of centrally mediated hypersomnia.

[Presynaptic histamine H3-receptors exist on cardiac sympathetic terminals of guinea pig].

This is the first time to report the existence of new presynaptic inhibitory autoreceptors--histamine H3-receptors in guinea pig myocardium. We found that (R)-alpha-methylhistamine (alpha-MeHA), a selective histamine H3-receptor agonist, attenuates the sympathetic inotropic response of isolated guinea pig atria elicited by electrical field stimulation. This inhibition was associated with a marked reduction in endogenous norepinephrine release. The above phenomenon was antagonised by selective histamine H3-receptor antagonists, and inhibited by pretreatment with N ethylmeleimide. The cardiac sympathetic response could be attenuated or facilitated by increase or decrease of endogenous histamine. Our findings indicate that the endogenous histamine might be involved in the modulation of cardiac sympathetic neurotransmission by interacting with histamine H3-receptors and the receptors are probably coupled to a G(o)/Gi protein.

The effect of REM sleep deprivation on histamine concentrations in different brain areas.

Rats were deprived of REM sleep (REMS) for 72 h with the platform method and decapitated in the morning immediately after the deprivation or in the afternoon after having been allowed 5 hours of rebound sleep. The histamine concentrations of the anterior and posterior hypothalamus, the cortex, the hippocampus and the pineal gland were measured, as well as the tele-methylhistamine concentrations of the anterior and posterior hypothalamus. Histamine concentrations were no different after REMS deprivation compared to large platform or dry cage controls, but in the anterior hypothalamus histamine levels increased during rebound sleep only in the REMS deprived rats. tele-Methylhistamine/histamine ratios were higher after 72 h of both REMS deprivation and the large platform treatment compared to dry cage controls, indicating increased histamine utilization during the platform treatment procedure.