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Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia

Saternos, Hannah C
http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731

Abstract Details

, Master of Science in Pharmaceutical Science (MSP), University of Toledo, Pharmaceutical Sciences (Pharmacology/Toxicology).
Primary endothelial cilia are mechanosensory organelles that are projected into the lumen of blood vessels. Defects in cilia assembly or function can lead to multiple human pathologies, collectively known as ciliopathies, including polycystic kidney disease and associated hypertension. Acetylcholine, a neurotransmitter, is implicated in essential hypertension in humans and animal models. It has been demonstrated that vascular endothelia require primary cilia to sense and transmit external mechanical stimuli into internal biochemical reactions. One of these reactions includes the biosynthesis and release of nitric oxide, which is one of the most potent endogenous vasodilators. Though both primary cilia and muscarinic acetylcholine receptors play important roles in vascular hypertension, their relationship has never been explored. To determine the roles of the cholinergic system and mechanosensory cilia, we studied the effects of acetylcholine on ciliary length and function in wild-type (WT) and mechano-insensitive cilia mutant endothelial cells (Pkd1-/- and Tg737orpk/orpk). AChMR activation significantly increases cilia length in endothelial cells treated with Ach (1.49±0.006 vs 3.46±0.02 for wild-type and 0.96±0.003 vs. 3.46±0.08 for Pkd1-/-) compared to control non-treated cells. We show for the first time that not only mouse vascular endothelia exhibit muscarinic receptor-type 1, 3 and 5 (AChM1-, 3-, and 5R) co-localization to primary cilia, but also kidney epithelia exhibit muscarinic receptor-type 1 and 3 colocalization to primary cilia. Data from AChMRs localization and expression experiments clearly points towards a role of AChMRs in cell division regulation and towards their involvement in the pathogenesis in PKD.
Wissam AbouAlaiwi (Committee Chair)
Youssef Sari (Committee Member)
William Messer Jr. (Committee Member)
Pharmacology

Recommended Citations

Citations

  • Saternos, H. C. (n.d.). Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731

    APA Style (7th edition)

  • Saternos, Hannah. Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia . University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731.

    MLA Style (8th edition)

  • Saternos, Hannah. "Newly Discovered Muscarinic Acetylcholine Receptors in the Primary Cilia ." Master's thesis, University of Toledo. Accessed APRIL 19, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=mco1468922731

    Chicago Manual of Style (17th edition)

mco1468922731
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.