Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine.
journal contributionposted on 2018-06-18, 00:00 authored by Dulari Jayawardena, Grace Guzman, Ravinder K. Gill, Waddah A. Alrefai, Hayat Onyüksel, Pradeep K. Dudeja
Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a broad array of physiological functions in many organs including the intestine. Its actions are mediated via G protein-coupled receptors, and vasoactive intestinal peptide receptor 1 (VPAC1) is the key receptor responsible for majority of VIP's biological activity. The distribution of VPAC1 along the length of the gastrointestinal tract and its subcellular localization in intestinal epithelial cells have not been fully characterized. The current studies were undertaken to determine VPAC1 distribution and localization so that VIP-based therapies can be targeted to specific regions of the intestine. The results indicated that the mRNA levels of VPAC1 showed an abundance pattern of colon > ileum > jejunum in the mouse intestine. In parallel, the VPAC1 protein levels were higher in the mouse colon, followed by the ileum and jejunum. Immunofluorescence studies in mouse colon demonstrated that the receptor was specifically localized to the luminal surface, as was evident by colocalization with the apical marker villin but not with the basolateral marker Na+/K+-ATPase. In the human intestine, VPAC1 mRNA expression exhibited a distribution similar to that in mouse intestine and was highest in the sigmoid colon. Furthermore, in the human colon, VPAC1 also showed predominantly apical localization. The physiological relevance of the expression and apical localization of VPAC1 remains elusive. We speculate that apical VPAC1 in intestinal epithelial cells may have relevance in recognizing secreted peptides in the intestinal lumen and therefore supports the feasibility of potential therapeutic and targeting use of VIP formulations via oral route to treat gastrointestinal diseases.NEW & NOTEWORTHY These studies for the first time present comprehensive data on the relative characterization of vasoactive intestinal peptide (VIP) receptors in the intestinal mucosa. Vasoactive intestinal peptide receptor 1 (VPAC1) was identified as the predominant receptor with higher levels in the colon compared with the small intestine and was mainly localized to the apical membrane. In addition, the findings in the human tissues were consistent with VPAC1 expression in the mouse intestine and open possibilities to target colonic tissues with VIP for treating diseases such as inflammatory bowel disease.
These studies were supported by the NIDDK grants R01 DK098170 (RKG), R01 DK54016, R01 DK81858, R01 DK92441 (PKD), R01 DK109709 (WAA) and the Department of Veterans Affairs BX 002011 (PKD) and BX000152 (WAA) and VA RCS Award (WAA) and VA SRCS Award (PKD) and TUBITAK Award (HO)
Publisher StatementCopyright @ American Physiological Society
CitationJayawardena, D., Guzman, G., Gill, R. K., Alrefai, W. A., Onyuksel, H. and Dudeja, P. K. Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2017. 313(1): G16-G25. 10.1152/ajpgi.00081.2017
PublisherAmerican Physiological Society