Publications

• Transport of histamine by vesicular monoamine transporter-2.

  Merickel A., Edwards R.H.

  Histamine mediates signalling by a wide range of neural and non-neural cells including mast cells. Like other biogenic amines, histamine is released from specialized secretory vesicles and requires transport from the cytoplasm into these vesicles. Of the two vesicular monoamine transporters, hista ... >> More

  Histamine mediates signalling by a wide range of neural and non-neural cells including mast cells. Like other biogenic amines, histamine is released from specialized secretory vesicles and requires transport from the cytoplasm into these vesicles. Of the two vesicular monoamine transporters, histamine potently inhibits 3H-serotonin transport by one (VMAT2) but not the other (VMAT1). In addition, histamine-containing cells in both neural and non-neural cells express VMAT2. However, histamine lacks the hydroxyl groups generally considered necessary for recognition as a substrate by the vesicular monoamine transporters. Using a heterologous expression system, we now report that VMAT2 not only shows inhibition by histamine but also transports 3H-histamine. Interestingly, histamine differs from other monoamine transmitters and does not inhibit 3H-reserpine binding to VMAT2, indicating interaction at a distinct site. Surprisingly, reserpine inhibits histamine transport with much less potency than serotonin transport, suggesting a different transport mechanism. However, replacement of serines in the third transmembrane domain of VMAT2 that have been shown to be essential for recognition of other monoamines also eliminate 3H-histamine transport, suggesting that these serine residues may do more than simply recognize the hydroxyl groups on a monoamine substrate. << Less

  Neuropharmacology 34:1543-1547(1995) [PubMed] [EuropePMC]

• Reserpine- and tetrabenazine-sensitive transport of (3)H-histamine by the neuronal isoform of the vesicular monoamine transporter.

  Erickson J.D., Eiden L.E., Schafer M.K., Weihe E.

  The transport of (3)H-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 of (3)H-histamine by both VMAT1 and VMAT2 was reserpine ... >> More

  The transport of (3)H-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 of (3)H-histamine by both VMAT1 and VMAT2 was reserpine-sensitive but only transport by VMAT2 was inhibited by tetrabenazine. Maximal equilibrated levels of (3)H-histamine accumulation by VMAT2 (K(m) 300 mu M) were approximately three times greater than that mediated by VMAT1 when using a subsaturating concentration of exogenous (3)H-histamine (50 mu M). 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. << Less

  J. Mol. Neurosci. 6:277-287(1995) [PubMed] [EuropePMC]

• The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors.

  Peter D., Jimenez J., Liu Y., Kim J., Edwards R.H.

  Classical studies using bovine chromaffin granules have defined the physiologic and pharmacologic properties of the vesicular amine transporter that packages monoamine transmitters into intracellular vesicles for subsequent regulated release. The recent isolation of two distinct but closely relate ... >> More

  Classical studies using bovine chromaffin granules have defined the physiologic and pharmacologic properties of the vesicular amine transporter that packages monoamine transmitters into intracellular vesicles for subsequent regulated release. The recent isolation of two distinct but closely related cDNA clones encoding vesicular amine transport suggests that the activity expressed in the brain (synaptic vesicle amine transporter or SVAT) may differ significantly from the previously described adrenal gland activity (chromaffin granule amine transporter or CGAT). A direct comparison of the two transporters now shows that SVAT has a higher affinity than CGAT for monoamine substrates, in particular for histamine. In addition, SVAT shows approximately 10-fold greater sensitivity to tetrabenazine than CGAT. [3H]Dihydrotetrabenazine shows no detectable binding to CGAT but does bind to SVAT, accounting for the differential sensitivity. Furthermore, methamphetamine preferentially inhibits transport by SVAT relative to CGAT, apparently by competing at the site of amine recognition rather than by disrupting the vesicular pH gradient. These previously unsuspected differences in the storage of monoamine transmitter in the central nervous system and the adrenal gland may help to account for several classic pharmacological observations. << Less

  J. Biol. Chem. 269:7231-7237(1994) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.