Autoradiography in mice reveals receptor expression in
sub-epithelial myofibroblasts.
Having confirmed the binding of
[125I]-hGLP-2(1-33,M10Y) to rodent GLP-2Rs, we did
autoradiography studies in mice with this radioligand. In all mice
examined (n=6), we observed strong labeling in the SEMFs of the
gastrointestinal (GI) tract (figure 5c,e and supplementary figure 2) and
in the islet cells of the endocrine pancreas (figure 5d,f and
supplementary figure 2). These data are consistent with previous data
(El-Jamal et al. 2014; De Heer et al. 2007; Ørskov et al. 2005), and
thereby confirming at the protein level what was shown at the level of
GLP-2R mRNA transcript. Injection of unlabeled GLP-2(1-33) prior to the
radioligand abrogated labeling in both tissues (figure 5e,f), supporting
the specific binding of
[125I]-hGLP-2(1-33,M10Y).
Since the pancreas is known for high expression levels of the GLP-1R and
given the observed binding of both hGLP-2-based radioligands to the
hGLP-1R (figure 4), we tested the binding of the radioligands to the
mouse and rat GLP-1R. Here, we were surprised by a very high specific
binding of both radioligands to the mouse GLP-1R (mGLP-1R), while no
binding was observed for the rat GLP-1R (rGLP-1R) (supplementary figure
3). The binding of both radioligands to mGLP-1R reached the same Emax as
for the mouse GLP-2R (mGLP-2R), but have a 32-fold lower affinity (table
2).