Coexpression of the mu‐opioid receptor splice variant MOR_1C and the vesicular glutamate transporter 2 (VGLUT2) in rat central nervous system

Abstract

It has been reported that mu-opioid agonists depress glutamate release in some neurons but the specific receptor subtype mediating this effect is unclear. The purpose of the present study was to examine whether a particular mu-opioid receptor (MOR) splice-variant, MOR(1C), is expressed in rat central nervous system (CNS) by terminals expressing the vesicular glutamate transporter2 (VGLUT2), a marker of glutamatergic neurons. Several MOR splice variants have been identified in mice and MOR(1C) appears mainly to be localized to fibers and terminals, from which most neurotransmitter release would be expected. In addition, VGLUT2 has been found in the CNS and antibodies to it are reliable markers for glutamatergic terminals. Using fluorescence immunohistochemistry and confocal microscopy to examine spatial relationships between MOR(1C) and VGLUT2, we found that MOR(1C) and VGLUT2 puncta were widely distributed throughout the rat CNS; moreover, many regions contained terminals that expressed both. Thus, it appears that coexpression of MOR(1C) and VGLUT2 is common in the rat CNS. We hypothesize that activation of MOR(1C) by mu-opioid agonists at some glutamatergic terminals may be a mechanism by which glutamate release is inhibited.

Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of OPRM1 in Brain Regions of C57BL/6 Mouse

“…While the exon 4 epitope was contained within a number of 7-TM variants (mMOR-1, mMOR-1H, mMOR-1I, and mMOR-1J) as well as a 6-TM variant (mMOR-1G) and the exon 7-encoded sequence is present in 7-TM variants (mMOR-1C, mMOR-1O, and mMOR-1U) as well as the 6-TM variant mMOR-1M, assigning a specific variant was not possible due to concurrent 5′ alternative splicing though the models dissociate the actions of different groups of C-terminal splice variants [38]. Other findings include that activation of mMOR-1C may be one mechanism by which glutamate release is inhibited, naloxone methiodide may represent a possible remedy for opioid-induced itching, MOR C-terminus phosphorylation does not appear to be critical for morphine tolerance in vivo and MOR-TRPV1 crosstalk in TRPV1 activation involves in morphine antinociception, tolerance and dependence [67][68][69][70]. Overall, analgesic effect of opioid agonist primarily results from exon 11-associated 6-TM variants [71], morphine-induced itch is mainly due to heterodimerization of 7-TM C-terminal variant mMOR-1D with gastrin-releasing peptide receptor and opioid-induced tolerance and physical dependence is partially dominated by mE7M (especially mMOR-1C and mMOR-1O at mRNA levels) and mE4M, respectively.…”

Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis

“…The guinea pig anti-VGluT1 recognizes amino acid residues 542–560 of rat VGluT1 (Melone et al, 2005; Ramer, 2008). The guinea pig anti-VGluT2 antibody recognizes amino acid residues 565–582 of rat VGluT2 (Ramer, 2008; Schnell and Wessendorf, 2008). Immunostaining for these antibodies was completely abolished when they were preadsorbed with the immunogen peptides (manufacturer’s technical information).…”

Differential content of vesicular glutamate transporters in subsets of vagal afferents projecting to the nucleus tractus solitarii in the rat

“…Both VGLUT antibodies were raised in guinea pig against immunogens specific to each transporter. The immunogen for anti-VGLUT1 was a peptide corresponding to amino acid residues 542-560 of rat VGLUT1 (Melone et al, 2005;Ramer, 2008a), and the immunogen for anti-VGLUT2 was a peptide corresponding to amino acid residues 565-582 of rat VGLUT2 (Schnell and Wessendorf, 2008;Ramer, 2008b). The specificity of these antibodies has been previously validated, and these antibodies have also been widely utilized (Chomsung et al, 2008;Hegarty et al, 2010).…”