Reserpine- and tetrabenazine-sensitive transport of3H-histamine by the neuronal isoform of the vesicular monoamine transporter
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The transport of3H-histamine by the endocrine-specific (VMAT1) and neuronal (VMAT2) isoforms of the vesicular monoamine transporter has been evaluated in digitonin-permeabilized fibroblasts transfected with either VMAT1 or VMAT2. Transport of3H-histamine by both VMAT1 and VMAT2 was reserpine-sensitive but only transport by VMAT2 was inhibited by tetrabenazine. Maximal equilibrated levels of3H-histamine accumulation by VMAT2 (K m∼300 µM) were approximately three times greater than that mediated by VMAT1 when using a subsaturating concentration of exogenous3H-histamine (50 µM). The expression of VMAT2 in histaminergic neurons in the rat brain was examined with polyclonal antipeptide antibodies specific for VMAT1 or VMAT2. VMAT2-positive and tyrosine hydroxylase-negative immunoreactive cell bodies were localized to the ventral part of the posterior hypothalamus in the region of the mamillary nuclei. The transport properties of VMAT2 and the distribution of VMAT2 in cell bodies in the tuberomammillary nucleus of the posterior hypothalamus reported here and the apparent absence of VMAT1 and VMAT2 in tissue mast cells support previous findings of reserpine-sensitive and reserpine-resistant pools of histamine in brain and peripheral tissues.
Index EntriesVesicular monoamine transporter isoforms VMAT1 VMAT2 histamine reserpine tetrabenazine posterior hypothalamus tuberomammillary nucleus mast cells
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