ArticlePeptides2013
Caveolae-dependent internalization and homologous desensitization of VIP/PACAP receptor, VPAC₂, in gastrointestinal smooth muscle.
Article in Peptides, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Loss of enteric BDNF-TrkB signaling and VIPergic dysfunction underlie gastrointestinal dysmotility in abioRxiv : the preprint server for biology · 2026Article
- Multi-faceted roles of β-arrestins in G protein-coupled receptor endocytosis.Nature communications · 2025Article
- Caveolin-1 Regulates Parathyroid Hormone (PTH)-Related Protein (PTHrP) Actions on PTH Receptor Type 1 in Bone Cells.Journal of cellular physiology · 2025Article
- A Cell Membrane-Level Approach to Cicatricial Alopecia Management: Is Caveolin-1 a Viable Therapeutic Target in Frontal Fibrosing Alopecia?Biomedicines · 2021Article
- The effect of Xenin25 on spontaneous circular muscle contractions of rat distal colon in vitro.Physiological reports · 2021Article
- Effect of Electroacupuncture on Bladder Dysfunction via Regulation of MLC and MLCK Phosphorylation in a Rat Model of Type 2 Diabetes Mellitus.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Caveolin1 Tyrosine-14 Phosphorylation: Role in Cellular Responsiveness to Mechanical Cues.The Journal of membrane biology · 2020Review
- An Overview of VPAC Receptors in Rheumatoid Arthritis: Biological Role and Clinical Significance.Frontiers in endocrinology · 2019Review
- The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus.International journal of molecular sciences · 2018Article
- Role of phosphatidylinositol-4,5-bisphosphate 3-kinase signaling in vesicular trafficking.Life sciences · 2016Review
- Genome-wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome.Neurogastroenterology and motility · 2016Article
- Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1-/- mice impair the peristaltic reflex and propulsion.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The main membrane proteins of caveolae (caveolin-1, -2 and -3) oligomerize within lipid rich domains to form regular invaginations of smooth muscle plasma membrane and participate in receptor internalization and desensitization independent of clathrin-coated vesicle endocytosis. We have previously shown that Gs-coupled VIP/PACAP receptors, VPAC2, predominantly expressed in smooth muscle cells of the gut, are exclusively phosphorylated by GRK2 leading to receptor internalization and desensitization. Herein, we characterized the role of caveolin-1 in VPAC2 receptor internalization and desensitization in gastric smooth muscle using three approaches: (i) methyl β-cyclodextrin (MβCD) to deplete cholesterol and disrupt caveolae in dispersed muscle cells, (ii) caveolin-1 siRNA to suppress caveolin-1 expression in cultured muscle cells, and (iii) caveolin-1 knockout mice (caveolin-1(-/-)). Pretreatment of gastric muscle cells with VIP stimulated tyrosine phosphorylation of caveolin-1, and induced VPAC2 receptor internalization (measured as decrease in (125)I-VIP binding after pretreatment) and desensitization (measured as decrease in VIP-induced cAMP formation after pretreatment). Caveolin-1 phosphorylation, and VPAC2 receptor internalization and desensitization were blocked by disruption of caveolae with MβCD, suppression of caveolin-1 with caveolin-1 siRNA or inhibition of Src kinase activity by PP2. Pretreatment with VIP significantly inhibited adenylyl cyclase activity and muscle relaxation in response to subsequent addition of VIP in freshly dispersed muscle cells and in muscle strips isolated from wild type and caveolin-1(-/-) mice; however, the inhibition was significantly attenuated in caveolin-1(-/-) mice. These results suggest that caveolin-1 plays an important role in VPAC2 receptor internalization and desensitization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.