Disease relevance of alpha-Methylhistamine

• Because steroids have been reported to modulate levels of guanine nucleotide-binding proteins, the lack of receptor specificity could reflect an indirect effect of steroids upon agonist binding and, in fact, we show that [3H]N alpha-methylhistamine binding to these cells, like somatostatin, is pertussis toxin-sensitive [1].
• N alpha-methylhistamine: association with Helicobacter pylori infection in humans and effects on gastric acid secretion [2].

High impact information on alpha-Methylhistamine

• Functional relevance of these H3-receptors was obtained by showing that transmural electrical stimulation of sympathetic nerve endings in human atrial tissue increased contractility, an effect blocked by propranolol and attenuated in a concentration-dependent manner by (R) alpha-methylhistamine [3].
• Histamine was a substrate for purified indolethylamine N-methyltransferase and unlike histamine N-methyltransferase which exclusively formed N tau-methylhistamine, indolethylamine N-methyltransferase catalyzed the in vitro formation of both N pi-methylhistamine and N alpha-methylhistamine [4].
• CONCLUSIONS: N alpha-Methylhistamine had no direct inhibitory effects on D-cells, but TNF-alpha both significantly reduced the cellular content and inhibited release [5].
• SKF92374 was also a weak competitive antagonist of N alpha-methylhistamine-induced inhibition of electrically induced contractions of the guinea pig ileum (Kd = 5.2 microM), an H3 receptor-mediated response [6].
• In rat brain cortex membranes, the specifically bound [3H]-N alpha-methylhistamine was monophasically displaced by clozapine (pKi 6.15) [7].

Chemical compound and disease context of alpha-Methylhistamine

• Helicobacter pylori, cultured on agar and in broth with and without added histamine, was found not to produce detectable levels of N alpha-methylhistamine [2].

Biological context of alpha-Methylhistamine

• Metoprine had only a very low affinity for H3 binding sites (labelled by 3H-N alpha-methylhistamine; pKi 4.46) [8].
• We have used [3H]N alpha-methylhistamine to characterize H3-binding in the guinea pig brain and to study its tissue distribution [9].
• Pretreatment with alpha-methylhistamine (100-300 nM) recuperated control level contractility and heart rate, and prevented the hypoxia-reoxygenation-induced leakage of creatine phosphokinase (CPK) [10].
• 3. In canine arteries, alpha-methylhistamine showed no vascular response, but in simian preparations, it caused a slight vasoconstriction [11].

Anatomical context of alpha-Methylhistamine

• Marked increase in [3H](R) alpha-methylhistamine binding in the superior colliculus of visually deprived rats after unilateral enucleation [12].
• This phenomenon was investigated by autoradiography of cryostat sections of rat forebrain labelled with [3H]N alpha-methylhistamine ([3H]NAMH, 4 nM) [13].
• The levels of [3H](R) alpha-methylhistamine binding sites in the denervated striatum (dorsomedial and dorsolateral) and substantia nigra were significantly higher than those in the contralateral side 21 days after nigral lesions [14].
• The localization of histamine H3-receptors in subcellular fractions from the rat brain was examined in a [3H] (R) alpha-methylhistamine binding assay and compared with those of histamine H1- and adrenaline alpha 1- and alpha 2-receptors [15].
• N alpha-Methylhistamine in gastric juice appears therefore to be associated with infection, although this product is not generated directly by the bacterium [2].

Associations of alpha-Methylhistamine with other chemical compounds

• We have found that (R) alpha-methylhistamine, the selective histamine H3-receptor agonist, attenuates the inotropic and chronotropic response of isolated guinea pig atria to transmural stimulation of adrenergic nerve endings [16].
• We determined the affinities of nordimaprit, homodimaprit, clobenpropit and imetit for H3 binding sites (labelled by 3H-N alpha-methylhistamine) in rat brain cortex homogenates and their potencies at presynaptic H3A receptors on noradrenergic nerve endings in mouse brain cortex slices [17].
• However, (R) alpha-methylhistamine affected neither the 5-HT nor the 5-HIAA level [18].
• The enhancement by thioperamide of pargyline-induced 5-HT accumulation was not inhibited by (R) alpha-methylhistamine [18].
• The cardiovascular responses to a series of selective histamine H3 receptor agonists, (R) alpha-methylhistamine, imetit and immepip and selective antagonists, thioperamide, clobenpropit and clophenpropit, were studied in anaesthetized rats [19].

Gene context of alpha-Methylhistamine

• N alpha-methylhistamine inhibits intestinal transit in mice by central histamine H1 receptor activation [20].
• In contrast, the histamine H3-receptor agonist alpha-methylhistamine (15 or 35 mumol/kg, i.v.) and the 5-HT1D receptor agonists sumatriptan (0.24 or 2.4 mumol/kg, i.v.) and CP 122,288 (0.0003-3 mumol/kg, i.v.) had no effect on these responses [21].
• [125I]Iodobolpyramine, [125I]iodoaminopotentine and [3H](R) alpha-methylhistamine were used as ligands to label H1, H2 and H3 receptors respectively [22].
• 3H-N alpha-Methylhistamine bound saturably to rat brain cortex homogenates with a Kd of 0.70 nmol/l and a Bmax of 98 fmol/mg protein [17].
• These results indicate that alpha-methylhistamine can be methylated as effectively as histamine, and may be a useful tool in further studies of HMT [23].

Analytical, diagnostic and therapeutic context of alpha-Methylhistamine

• The selective H3-agonist, alpha-methylhistamine (alpha-MeHA, 1-10 mg/kg i.v.) did not alter basal respiratory insufflation pressure, but reduced the NANC bronchoconstrictor response to vagal stimulation in dose-dependent manner (with a maximal inhibition of 46.0 +/- 10.3%; mean +/- S.E. at 10 mg/kg) (P less than 0.02) [24].
• Major [3H](R) alpha-methylhistamine binding sites with increased specific activities ([3H]ligand binding vs. protein amount) were recovered from the P2 fraction by differential centrifugation [15].
• Gastric juice and tissue biopsies from infected patients have been analysed for the presence of N alpha-methylhistamine using a specific and sensitive assay based on gas chromatography mass spectrometry [2].
• Using a modified HPLC method with a fluorescence spectrophotometer and a weak cation exchanger, it was possible to separate (R)-alpha-methylhistamine (alpha-methylhistamine) from histamine in plasma and various tissues [25].
• Several studies suggesting that (R) alpha-methylhistamine might find various clinical applications, it was submitted to toxicological studies and initial clinical trials [26].

References