ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2008
Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 167 citations in OpenAlex.
- Primary cilia: sensors of biliary homeostasis and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- AKAP2/PKA complex coordinates primary ciliogenesis, ciliary trafficking and Shh signaling.Cell communication and signaling : CCS · 2026Article
- The exocyst in ciliogenesis.Renal failure · 2025Review
- Primary cilia function as hubs for signal transduction.Cell & bioscience · 2025Review
- The primary cilium as a multifunctional organelle: emerging roles and unanswered questions.Cell communication and signaling : CCS · 2025Review
- Primary Cilia and Cardiovascular Risk Factors in Alzheimer's Disease.Brain sciences · 2025Review
- Cholangiocytes' primary cilia regulate DNA damage response and repair.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Review
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
- Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.Advanced healthcare materials · 2023Review
- A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.Science translational medicine · 2023Article
- NOTCH signalling - a core regulator of bile duct disease?Disease models & mechanisms · 2023Review
- Primary cilia as dynamic and diverse signalling hubs in development and disease.Nature reviews. Genetics · 2023Review
- Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets.Frontiers in molecular biosciences · 2023Review
- Role of the microtubules in the electrical activity of the primary cilium of renal epithelial cells.Frontiers in molecular biosciences · 2023Article
- Compartmentalised cAMP signalling in the primary cilium.Frontiers in physiology · 2023Review
- Genetics, pathobiology and therapeutic opportunities of polycystic liver disease.Nature reviews. Gastroenterology & hepatology · 2022Review
- Polycystic Liver Disease: Advances in Understanding and Treatment.Annual review of pathology · 2022Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Cholangiocytes, the epithelial cells lining intrahepatic bile ducts, contain primary cilia, which are mechano- and osmosensory organelles detecting changes in bile flow and osmolality and transducing them into intracellular signals. Here, we asked whether cholangiocyte cilia are chemosensory organelles by testing the expression of P2Y purinergic receptors and components of the cAMP signaling cascade in cilia and their involvement in nucleotide-induced cAMP signaling in the cells. We found that P2Y(12) purinergic receptor, adenylyl cyclases (i.e., AC4, AC6, and AC8), and protein kinase A (i.e., PKA RI-beta and PKA RII-alpha regulatory subunits), exchange protein directly activated by cAMP (EPAC) isoform 2, and A-kinase anchoring proteins (i.e., AKAP150) are expressed in cholangiocyte cilia. ADP, an endogenous agonist of P2Y(12) receptors, perfused through the lumen of isolated rat intrahepatic bile ducts or applied to the ciliated apical surface of normal rat cholangiocytes (NRCs) in culture induced a 1.9- and 1.5-fold decrease of forskolin-induced cAMP levels, respectively. In NRCs, the forskolin-induced cAMP increase was also lowered by 1.3-fold in response to ATP-gammaS, a nonhydrolyzed analog of ATP but was not affected by UTP. The ADP-induced changes in cAMP levels in cholangiocytes were abolished by chloral hydrate (a reagent that removes cilia) and by P2Y(12) siRNAs, suggesting that cilia and ciliary P2Y(12) are involved in nucleotide-induced cAMP signaling. In conclusion, cholangiocyte cilia are chemosensory organelles that detect biliary nucleotides through ciliary P2Y(12) receptors and transduce corresponding signals into a cAMP response.
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