Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine

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..

Medienart:

Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:313

Enthalten in:

American journal of physiology / Gastrointestinal and liver physiology - 313(2017), 1, Seite G16

Sprache:

Englisch

Beteiligte Personen:

Dulari Jayawardena [VerfasserIn]
Grace Guzman [Sonstige Person]
Ravinder K Gill [Sonstige Person]
Waddah A Alrefai [Sonstige Person]
Hayat Onyuksel [Sonstige Person]
Pradeep K Dudeja [Sonstige Person]

Links:

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Themen:

Biological activity
Cells
Colon
Digestive system
Epithelial cells
Fluorescence
G protein-coupled receptors
Gastrointestinal tract
Gastrointestinal tract diseases
Gene expression
Ileum
Immunofluorescence
Intestine
Jejunum
Localization
Na+/K+-exchanging ATPase
Peptides
Proteins
Ribonucleic acid--RNA
Vasoactive agents
Vasoactive intestinal peptide

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC1997635054