Differential expression of two vesicular monoamine transporters

Abstract

Specific transport proteins package classical neurotransmitters into vesicles so that their release can be regulated by neural activity. Previous studies have suggested that a single activity mediates the vesicular transport of monoamines in the adrenal gland, brain, and other tissues such as mast cells and platelets. However, molecular cloning has recently identified two vesicular transporters for monoamines. Although the predicted proteins are closely related in sequence, they show a range of differences in their physiologic and pharmacologic properties. To clarify further the biological significance of the observed functional differences, we have generated anti-peptide antibodies to the C-termini of the two transporters and used them to determine the distribution and localization of the proteins in the rat. We have detected expression of vesicular monoamine transporter 1 (VMAT1) in adrenal chromaffin cells but not in neural cells. Interestingly, some adrenal chromaffin cells also express VMAT2 but the amount of VMAT2 relative to VMAT1 appears much lower than in the bovine adrenal gland. In contrast, sympathetic ganglion cells express only VMAT2, as do enteric neurons and enterochromaffin-like cells of the stomach. Thus, although adrenal chromaffin cells, sympathetic and enteric neurons derive from the neural crest, they express different vesicular amine transporters. In the CNS, dopamine, norepinephrine, epinephrine, 5-HT, and histamine cell groups all express VMAT2. These findings are consistent with the functional characteristics of VMAT1 and VMAT2 and help to explain several classic pharmacological observations. VMAT2-immunoreactivity is generally stronger in cell bodies, proximal dendrites and axonal processes, indicating the potential for monoamine storage at each of these sites. Surprisingly, dopaminergic interneurons in the olfactory bulb show no detectable immunoreactivity for either VMAT1 or VMAT2.

Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour

“…Additionally, compared with the constitutive VMAT2-KO mice, histamine neuro transmission remained intact in our models. The presence of histamine, a potent regulator of digestive function, 8,9,34,35 could also explain the lengthened survival from a few days to 3 weeks in the VMAT2 DATcre -KO mice. Whereas the monoamine releaser amphetamine was able to rescue the death of constitutive VMAT2-KO mice before weaning, 11 it had deleterious effects on the survival of the VMAT2 DATcre -KO mice.…”

“…VMAT1 is primarily expressed in the peripheral nervous system; VMAT2 is primarily expressed in the neurons of the central nervous system. 8,9 The functions of VMAT2 include storage of monoamines, protection of monoamines from cytoplasmic oxi dation and regulation of stimulated monoamine quantal release. 10 Thus, VMAT2 deficiency contributes to a decrease in the synaptic release of monoamines and an increase in the degradation of intracellular monoamines.…”

Distribution of Vesicular Monoamine Transporter 2 Protein in Human Brain: Implications for Brain Imaging Studies

“…The multiple bands (I, IIa, IIb, III, IV) of VMAT2 detected by the commonly used C-terminus antibodies (AB1767 used in this study and another similar antibody AB1598P from Chemicon, initially developed by Erickson et al (1996) and Edwards and colleagues (Peter et al, 1995), respectively) and their uncertain identity have been a major challenge for quantitative studies of VMAT2 protein in the brain. Many studies thus chose to examine only the major band detected (Sandoval et al, 2002;Haycock et al, 2003;Little et al, 2003;Gonzalez-Hernandez et al, 2004;Fortune and Lurie, 2009), which in most cases has been the mature band I (Wang et al, 1997;Miller et al, 1999;Haycock et al, 2003;Little et al, 2003;Gonzalez-Hernandez et al, 2004;Jassen et al, 2005;Cruz-Muros et al, 2008) although in a few instances a 55-kDa band was found to be the major band in rodent brains (Holtje et al, 2003;Duchemin et al, 2009;Fortune and Lurie, 2009).…”

Innervation of ectopic endometrium in a rat model of endometriosis

“…CGRP and SP are generally considered to be specific markers for C and A␦ sensory fibers (11,12). In contrast, VMAT2 is expressed in monoamine-containing neurons and fibers, including sympathetic nerves (16), and the antibody produces immunostaining similar to that produced by other markers for sympathetic nerves (e.g., tyrosine hydroxylase; ref. 15).…”