Presynaptic localization of histamine H3-receptors in rat brain.
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. 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. Minor [3H](R)alpha-methylhistamine binding sites with increased specific activities were also detected in the P3 fraction. Further subfractionation of the P2 fraction by discontinuous sucrose density gradient centrifugation showed major recoveries of [3H](R)alpha-methylhistamine binding in myelin (MYE) and synaptic plasma membrane (SPM) fractions. A further increase in specific activity was observed in the MYE fraction, but the SPM fraction showed no significant increase in specific activity. Adrenaline alpha 2-receptors, the pre-synaptic autoreceptors, in a [3H] yohimbine binding assay showed distribution patterns similar to histamine H3-receptors. On the other hand, post-synaptic histamine H1- and adrenaline alpha 1-receptors were closely localized and distributed mainly in the SPM fraction with increased specific activity. Only a negligible amount was recovered in the MYE fraction, unlike the histamine H3- and adrenaline alpha 2-receptors.
Fujimoto
K
K
Department of Pharmacology II, Faculty of Medicine, Osaka University, Japan.
Mizuguchi
H
H
Fukui
H
H
Wada
H
H
D000818:Animals; D001921:Brain / Q000502:physiology*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D007700:Kinetics; D008761:Methylhistamines / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011968:Receptors, Histamine / Q000302:isolation & purification / Q000378:metabolism*; D018100:Receptors, Histamine H3; D013569:Synapses / Q000502:physiology*; D014316:Tritium
D008761:Methylhistamines; D011942:Receptors, Adrenergic, alpha; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D014316:Tritium; C048140:N-methylhistamine