e061b8fb5e8af7272f3f1162ac5ded1d 327370.pdf 8b975fde6e7a7dd2cc1b98d38c90a7148cfea826 327370.pdf 93f02b71fb6f6c0a92638dc43c5b3498cb4ce2fb0b73f7410869b25bc5bfe19b 327370.pdf Title: Alternative Pathways of Acetylcholine Release in the Colon: Role of High‐Affinity Choline Transporters Subject: Neurogastroenterology Motil 2026.38:e70280 Keywords: Keywords: acetylcholine; choline transporter; colon; high affinity; organic cation transporter; smooth muscle contraction Author: A. Martinez-Daunis,B. Yordanova, S. Traserra, P. Vergara, M. Jimenez Creator: Adobe InDesign 19.5 (Windows) Producer: Adobe PDF Library 17.0; modified using iTextSharp 5.5.13.4 ©2000-2024 iText Group NV (AGPL-version) CreationDate: Sat Mar 7 15:23:59 2026 CET ModDate: Tue Apr 14 11:52:28 2026 CEST Custom Metadata: yes Metadata Stream: yes Tagged: yes UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 782.362 pts Page rot: 0 File size: 841365 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OJTEJV+STIXTwoText Type 1C Custom yes yes yes 42 0 CHQFXT+STIXTwoText-BoldItalic Type 1C WinAnsi yes yes yes 1244 0 BVDEJV+STIXTwoText-Italic Type 1C WinAnsi yes yes yes 44 0 FEASNN+ArialRoundedMTBold Type 1C WinAnsi yes yes no 1245 0 JCAVRF+STIXTwoText-Bold Type 1C Custom yes yes yes 43 0 Times-Roman Type 1 WinAnsi no no no 5 0 EFLMZP+STIX-Regular Type 1C Custom yes yes yes 61 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 88 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 89 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 103 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 104 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 115 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 116 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 117 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 118 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 119 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 120 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 130 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 131 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 144 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 145 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 146 0 ENJMZP+Arial-BoldMT Type 1C WinAnsi yes yes no 147 0 GQNYBL+ArialMT Type 1C WinAnsi yes yes no 148 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-04-15 03:59:01 CEST RepresentationInformation: 327370.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-04-14 12:02:16 CEST Size: 841365 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 2 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: true NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Language: en-US Outlines: Item: Title: Alternative Pathways of Acetylcholine Release in the Colon: Role of High-Affinity Choline Transporters Children: Item: Title: ABSTRACT Item: Title: Key Points Item: Title: 1   |   Introduction Item: Title: 2   |   Materials and Methods Children: Item: Title: 2.1   |   Ethics Statement Item: Title: 2.2   |   Animals and Tissue Preparation Item: Title: 2.3   |   Mechanical Studies Item: Title: 2.4   |   Experiments Children: Item: Title: 2.4.1   |   Experiment 1 Item: Title: 2.4.2   |   Experiment 2 Item: Title: 2.4.3   |   Experiment 3 Item: Title: 2.4.4   |   Experiment 4 Item: Title: 2.4.5   |   Experiment 5 Item: Title: 2.5   |   Measurements Item: Title: 2.6   |   Statistics Item: Title: 2.7   |   Drugs and Solutions Item: Title: 2.8   |   Correlation With Single-Cell RNA Analysis Item: Title: 3   |   Results Children: Item: Title: 3.1   |   Experiment 1. Neural Release of Acetylcholine Item: Title: 3.2   |   Experiment 2. Full-Thickness vs. Isolated Circular Muscle Responses Item: Title: 3.3   |   Experiment 3. Neostigmine Responses: Effects of Hemicholinium-3, Corticosterone, and Hexamethonium Item: Title: 3.4   |   Experiment 4. Effect of Hemicholinium-3 in the Presence of ω-CTX Item: Title: 3.5   |   Experiment 5. Effect of Neostigmine Following Pre-Incubation With Hemicholinium-3, Corticosterone, and Hexamethonium Item: Title: 3.6   |   Correlation With Single Cell RNA Analysis Item: Title: 4   |   Discussion Item: Title: 5   |   Conclusion Item: Title: Author Contributions Item: Title: Acknowledgments Item: Title: Conflicts of Interest Item: Title: Data Availability Statement Item: Title: References Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode FilterPipeline: CCITTFaxDecode Images: Image: NisoImageMetadata: FormatName: image/png ImageWidth: 228 ImageHeight: 45 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 177 ImageHeight: 40 ColorSpace: CMYK BitsPerSample: 8 BitsPerSampleUnit: integer Intent: RelativeColorimetric Name: X Image: NisoImageMetadata: FormatName: image/tiff CompressionScheme: CCITT Group 4 ImageWidth: 517 ImageHeight: 108 BitsPerSample: 1 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FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true XMP: application/pdfdoi:10.1111/nmo.70280 10.1111/nmo.70280https://doi.org/10.1111/nmo.70280 2026-03-07trueonlinelibrary.wiley.com10.1111/nmo.70280 onlinelibrary.wiley.comtrue10.1111/nmo.702802026-03-07 VoR Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/nmo.70280 for your more information Rect: 45, 25, 155, 14 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/nmo.70280 for your more information Rect: 158, 676, 213, 661 Annotation: Subtype: Link Contents: Department of Cell Biology, Physiology and Immunology and Neurosciences InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain Rect: 122, 586, 125, 573 ActionDest: 207 Annotation: Subtype: Link Contents: Department of Cell Biology, Physiology and Immunology and Neurosciences InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain Rect: 188, 586, 191, 573 ActionDest: 207 Annotation: Subtype: Link Contents: Department of Cell Biology, Physiology and Immunology and Neurosciences InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain Rect: 244, 586, 247, 573 ActionDest: 207 Annotation: Subtype: Link Contents: Department of Cell Biology, Physiology and Immunology and Neurosciences InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain Rect: 297, 586, 305, 573 ActionDest: 207 Annotation: Subtype: Link Contents: Department of Cell Biology, Physiology and Immunology and Neurosciences InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain Rect: 360, 586, 369, 573 ActionDest: 207 Annotation: Subtype: Link Contents: Please visit https://orcid.org/0000-0002-6602-7332 for your more information Rect: 369, 587, 381, 575 Annotation: Subtype: Link Contents: Please visit mailto:marcel.jimenez@uab.cat for your more information Rect: 148, 531, 228, 520 Annotation: Subtype: Link Contents: B. T.Drumm, B. E.Rembetski, K.Huynh, A.Nizar, S. A.Baker, and K. M.Sanders, “Excitatory Cholinergic Responses in Mouse Colon Intramuscular Interstitial Cells of Cajal Are due to Enhanced Ca2+ Release via M3 Receptor Activation,” FASEB Journal34, no. 8 (2020): 10073 10095, https://doi.org/10.1096/fj.202000672R. Rect: 447, 205, 461, 192 ActionDest: 152 Annotation: Subtype: Link Contents: Please visit http://creativecommons.org/licenses/by/4.0/ for your more information Rect: 202, 78, 297, 68 Annotation: Subtype: Link Rect: 519, 782, 595, 767 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Contents: M. R.Bennett, L.Farnell, W. G.Gibson, and N. A.Lavidis, “Synaptic Transmission at Visualized Sympathetic Boutons: Stochastic Interaction Between Acetylcholine and Its Receptors,” Biophysical Journal72, no. 4 (1997): 1595 1606, https://doi.org/10.1016/S00063495(97)788064. Rect: 161, 521, 166, 508 ActionDest: 152 Annotation: Subtype: Link Contents: D. V.Abramochkin, L. F.Nurullin, A. A.Borodinova, etal., “NonQuantal Release of Acetylcholine From Parasympathetic Nerve Terminals in the Right Atrium of Rats,” Experimental Physiology95, no. 2 (2010): 265 273, https://doi.org/10.1113/expphysiol.2009.050302. Rect: 258, 475, 272, 462 ActionDest: 152 Annotation: Subtype: Link Contents: L.Traeger, N.DudiVenkata, S.Bedrikovetski, H. M.Kroon, J. W.Moore, and T.Sammour, “Use of Acetylcholinesterase Inhibitors in Reducing Time to Gastrointestinal Function Recovery Following Abdominal Surgery: A Systematic Review,” Digestive Surgery41, no. 1 (2024): 12 23, https://doi.org/10.1159/000535753. Rect: 48, 245, 52, 232 ActionDest: 152 Annotation: Subtype: Link Contents: T.Arthur and A.Burgess, “Acute Colonic PseudoObstruction,” Clinics in Colon and Rectal Surgery35, no. 3 (2022): 221 226, https://doi.org/10.1055/s00411740044. Rect: 48, 233, 52, 220 ActionDest: 152 Annotation: Subtype: Link Contents: S.Traserra, L. G.AlcaláGonzález, C.Barber, etal., “New Insights Into the Characterization of the Mechanism of Action of Hyoscine Butylbromide in the Human Colon ExVivo,” European Journal of Pharmacology972 (2024): 176550, https://doi.org/10.1016/j.ejphar.2024.176550. Rect: 224, 141, 237, 128 ActionDest: 152 Annotation: Subtype: Link Contents: J.Beckmann and K. S.Lips, “The NonNeuronal Cholinergic System in Health and Disease,” Pharmacology92, no. 5 6 (2013): 286 302, https://doi.org/10.1159/000355835. Rect: 198, 107, 220, 94 ActionDest: 152 Annotation: Subtype: Link Contents: S.Bader, J.Klein, and M.Diener, “Choline Acetyltransferase and Organic Cation Transporters Are Responsible for Synthesis and PropionateInduced Release of Acetylcholine in Colon Epithelium,” European Journal of Pharmacology733 (2014): 23 33, https://doi.org/10.1016/j.ejphar.2014.03.036. Rect: 456, 740, 464, 727 ActionDest: 152 Annotation: Subtype: Link Contents: T. E.Billipp, C.Fung, L. M.Webeck, etal., “Tuft CellDerived Acetylcholine Promotes Epithelial Chloride Secretion and Intestinal Helminth Clearance,” Immunity57, no. 6 (2024): 1243 1259.e8, https://doi.org/10.1016/j.immuni.2024.03.023. Rect: 496, 717, 504, 704 ActionDest: 152 Annotation: Subtype: Link Contents: T. E.Billipp, C.Fung, L. M.Webeck, etal., “Tuft CellDerived Acetylcholine Promotes Epithelial Chloride Secretion and Intestinal Helminth Clearance,” Immunity57, no. 6 (2024): 1243 1259.e8, https://doi.org/10.1016/j.immuni.2024.03.023. Rect: 461, 659, 483, 647 ActionDest: 152 Annotation: Subtype: Link Contents: E.Alberti, H. B.Mikkelsen, J. O.Larsen, and M.Jiménez, “Motility Patterns and Distribution of Interstitial Cells of Cajal and Nitrergic Neurons in the Proximal, Mid, and Distal Colon of the Rat,” Neurogastroenterology and Motility17, no. 1 (2005): 133 147, https://doi.org/10.1111/j.13652982.2004.00603.x. Rect: 370, 210, 378, 198 ActionDest: 152 Annotation: Subtype: Link Contents: Please see "table 1" for your more reference Rect: 472, 164, 476, 152 ActionDest: 59 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Contents: Please see "table 1" for your more reference Rect: 204, 314, 209, 301 ActionDest: 59 Annotation: Subtype: Link Contents: Please refer footnote number a Rect: 457, 704, 460, 692 ActionDest: 59 Annotation: Subtype: Link Contents: Please refer footnote number a Rect: 457, 653, 460, 640 ActionDest: 59 Annotation: Subtype: Link Contents: Please refer footnote number a Rect: 510, 636, 513, 623 ActionDest: 59 Annotation: Subtype: Link Contents: Please refer footnote number b Rect: 527, 625, 530, 612 ActionDest: 59 Annotation: Subtype: Link Contents: Please refer footnote number a Rect: 510, 573, 513, 561 ActionDest: 59 Annotation: Subtype: Link Contents: Please refer footnote number b Rect: 527, 562, 530, 549 ActionDest: 59 Annotation: Subtype: Link Contents: Please refer footnote number a Rect: 510, 522, 513, 509 ActionDest: 59 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Contents: Please visit https://www.sigmaaldrich.com/ES/es/substance/neostigminebromide30320114807 for your more information Rect: 77, 374, 160, 361 Annotation: Subtype: Link Contents: Please visit https://singlecell.broadinstitute.org/single_cell for your more information Rect: 60, 202, 239, 189 Annotation: Subtype: Link Contents: L.Tarhan, J.Bistline, J.Chang, B.Galloway, E.Hanna, and E.Weitz, “Single Cell Portal: An Interactive Home for SingleCell Genomics Data,” bioRxiv (2023): 2023.07.13.548886, https://doi.org/10.1101/2023.07.13.548886. Rect: 244, 202, 252, 189 ActionDest: 152 Annotation: Subtype: Link Contents: Please see "figure 1" for your more reference Rect: 514, 717, 518, 704 ActionDest: 84 Annotation: Subtype: Link Contents: Please see "figure 1" for your more reference Rect: 466, 682, 470, 670 ActionDest: 84 Annotation: Subtype: Link Contents: Please see "figure 2" for your more reference Rect: 508, 556, 512, 543 ActionDest: 102 Annotation: Subtype: Link Contents: Please see "figure 2" for your more reference Rect: 467, 510, 471, 497 ActionDest: 102 Annotation: Subtype: Link Contents: Please see "figure 3" for your more reference Rect: 360, 410, 364, 397 ActionDest: 114 Annotation: Subtype: Link Contents: Please see "figure 3" for your more reference Rect: 415, 203, 419, 190 ActionDest: 114 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Contents: Please see "figure 4" for your more reference Rect: 102, 119, 106, 106 ActionDest: 129 Annotation: Subtype: Link Contents: Please see "figure 4" for your more reference Rect: 149, 73, 153, 60 ActionDest: 129 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Contents: Please see "figure 5" for your more reference Rect: 230, 130, 235, 117 ActionDest: 143 Annotation: Subtype: Link Contents: L.Tarhan, J.Bistline, J.Chang, B.Galloway, E.Hanna, and E.Weitz, “Single Cell Portal: An Interactive Home for SingleCell Genomics Data,” bioRxiv (2023): 2023.07.13.548886, https://doi.org/10.1101/2023.07.13.548886. Rect: 163, 65, 171, 52 ActionDest: 152 Annotation: Subtype: Link Contents: Figure S1: Dotplot showing the % and mean expression of different genes (Right column) in different cell types (Top). The dot plot shows the % of cells from a particular group that express on gene and the scaled mean expression is the mean intensity of expression. Data published in single cell portal obtained from mouse large intestine (https://singlecell.broadinstitute.org/single_cell/study/SCP1038/thehumanandmouseentericnervoussystematsinglecellresolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=&annotation=LABELgroupcluster&subsample=100000) [25]. Avil and Dclk1 are the mRNA of the gene encoding Advilin and doublecortin like Kinase 1 which both are markers of Tuftt cells in rodents. ChAT is the mRNA of genes encoding Choline acetyltransferase. Notice its expression in Neurons and Tuft Cells. Slc5a7 is the RNAm of the gene encoding the High affinity choline transporter 1 which is highly expressed in neurons. Slc22a1, 2 and 13 are the mRNA of the genes encoding OCTs 1, 2 and 3 respectively. Chrm3 is the mRNA of the gene encoding cholinergic receptor muscarinic 3. Rect: 386, 222, 395, 209 ActionDest: 181 Annotation: Subtype: Link Contents: Figure S1: Dotplot showing the % and mean expression of different genes (Right column) in different cell types (Top). The dot plot shows the % of cells from a particular group that express on gene and the scaled mean expression is the mean intensity of expression. Data published in single cell portal obtained from mouse large intestine (https://singlecell.broadinstitute.org/single_cell/study/SCP1038/thehumanandmouseentericnervoussystematsinglecellresolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=&annotation=LABELgroupcluster&subsample=100000) [25]. Avil and Dclk1 are the mRNA of the gene encoding Advilin and doublecortin like Kinase 1 which both are markers of Tuftt cells in rodents. ChAT is the mRNA of genes encoding Choline acetyltransferase. Notice its expression in Neurons and Tuft Cells. Slc5a7 is the RNAm of the gene encoding the High affinity choline transporter 1 which is highly expressed in neurons. Slc22a1, 2 and 13 are the mRNA of the genes encoding OCTs 1, 2 and 3 respectively. Chrm3 is the mRNA of the gene encoding cholinergic receptor muscarinic 3. Rect: 419, 188, 428, 175 ActionDest: 181 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Contents: D. V.Abramochkin, L. F.Nurullin, A. A.Borodinova, etal., “NonQuantal Release of Acetylcholine From Parasympathetic Nerve Terminals in the Right Atrium of Rats,” Experimental Physiology95, no. 2 (2010): 265 273, https://doi.org/10.1113/expphysiol.2009.050302. Rect: 129, 176, 172, 163 ActionDest: 152 Annotation: Subtype: Link Contents: J. I.Gillespie, M.vanMarkerinkIttersum, and J.De Vente, “Interstitial Cells and Cholinergic Signalling in the Outer Muscle Layers of the GuineaPig Bladder,” BJU International97, no. 2 (2006): 379 385, https://doi.org/10.1111/j.1464410X.2006.05989.x. Rect: 180, 130, 189, 117 ActionDest: 181 Annotation: Subtype: Link Contents: A.MartínezDaunis, M.Sorribas, S.Traserra, etal., Cholinergic Tuft Cells and Their Role in Secretory Responses Across Species [poster NGS2167290]. Presented at: NeuroGastro 2025 (European Society of Neurogastroenterology and Motility, 2025). Rect: 343, 165, 353, 152 ActionDest: 181 Annotation: Subtype: Link Contents: E.Alberti, H. B.Mikkelsen, J. O.Larsen, and M.Jiménez, “Motility Patterns and Distribution of Interstitial Cells of Cajal and Nitrergic Neurons in the Proximal, Mid, and Distal Colon of the Rat,” Neurogastroenterology and Motility17, no. 1 (2005): 133 147, https://doi.org/10.1111/j.13652982.2004.00603.x. Rect: 344, 153, 353, 140 ActionDest: 152 Annotation: Subtype: Link Contents: D. V.Abramochkin, A. A.Borodinova, L. V.Rosenshtraukh, and E. E.Nikolsky, “Both Neuronal and NonNeuronal Acetylcholine Take Part in NonQuantal Acetylcholine Release in the Rat Atrium,” Life Sciences91, no. 21 22 (2012): 1023 1026, https://doi.org/10.1016/j.lfs.2012.03.031. Rect: 421, 107, 460, 94 ActionDest: 181 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Contents: D. E.Burleigh and S. J.Trout, “Morphine Attenuates Cholinergic Nerve Activity in Human Isolated Colonic Muscle,” British Journal of Pharmacology88, no. 2 (1986): 307 313, https://doi.org/10.1111/j.14765381.1986.tb10206.x. Rect: 274, 176, 283, 163 ActionDest: 181 Annotation: Subtype: Link Contents: S.Traserra, L. G.AlcaláGonzález, C.Barber, etal., “New Insights Into the Characterization of the Mechanism of Action of Hyoscine Butylbromide in the Human Colon ExVivo,” European Journal of Pharmacology972 (2024): 176550, https://doi.org/10.1016/j.ejphar.2024.176550. Rect: 48, 141, 52, 128 ActionDest: 152 Annotation: Subtype: Link Contents: Please see "figure 2 5" for your more reference Rect: 188, 61, 202, 48 ActionDest: 102 Annotation: Subtype: Link Contents: D. E.Burleigh and S. J.Trout, “Morphine Attenuates Cholinergic Nerve Activity in Human Isolated Colonic Muscle,” British Journal of Pharmacology88, no. 2 (1986): 307 313, https://doi.org/10.1111/j.14765381.1986.tb10206.x. Rect: 308, 498, 317, 486 ActionDest: 181 Annotation: Subtype: Link Contents: D. V.Abramochkin, L. F.Nurullin, A. A.Borodinova, etal., “NonQuantal Release of Acetylcholine From Parasympathetic Nerve Terminals in the Right Atrium of Rats,” Experimental Physiology95, no. 2 (2010): 265 273, https://doi.org/10.1113/expphysiol.2009.050302. Rect: 369, 429, 395, 417 ActionDest: 152 Annotation: Subtype: Link Contents: Figure S1: Dotplot showing the % and mean expression of different genes (Right column) in different cell types (Top). The dot plot shows the % of cells from a particular group that express on gene and the scaled mean expression is the mean intensity of expression. Data published in single cell portal obtained from mouse large intestine (https://singlecell.broadinstitute.org/single_cell/study/SCP1038/thehumanandmouseentericnervoussystematsinglecellresolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=&annotation=LABELgroupcluster&subsample=100000) [25]. Avil and Dclk1 are the mRNA of the gene encoding Advilin and doublecortin like Kinase 1 which both are markers of Tuftt cells in rodents. ChAT is the mRNA of genes encoding Choline acetyltransferase. Notice its expression in Neurons and Tuft Cells. Slc5a7 is the RNAm of the gene encoding the High affinity choline transporter 1 which is highly expressed in neurons. Slc22a1, 2 and 13 are the mRNA of the genes encoding OCTs 1, 2 and 3 respectively. Chrm3 is the mRNA of the gene encoding cholinergic receptor muscarinic 3. Rect: 538, 383, 546, 371 ActionDest: 181 Annotation: Subtype: Link Contents: I.Wessler, E.Roth, C.Deutsch, etal., “Release of NonNeuronal Acetylcholine From the Isolated Human Placenta Is Mediated by Organic Cation Transporters,” British Journal of Pharmacology134, no. 5 (2001): 951 956. Rect: 432, 303, 441, 290 ActionDest: 181 Annotation: Subtype: Link Contents: P.Mandl and J. P.Kiss, “Inhibitory Effect of Hemicholinium3 on Presynaptic Nicotinic Acetylcholine Receptors Located on the Terminal Region of Myenteric Motoneurons,” Neurochemistry International49, no. 4 (2006): 327 333, https://doi.org/10.1016/j.neuint.2006.03.001. Rect: 366, 211, 375, 198 ActionDest: 181 Page: Sequence: 9 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Contents: S.Traserra, L. G.AlcaláGonzález, C.Barber, etal., “New Insights Into the Characterization of the Mechanism of Action of Hyoscine Butylbromide in the Human Colon ExVivo,” European Journal of Pharmacology972 (2024): 176550, https://doi.org/10.1016/j.ejphar.2024.176550. Rect: 201, 613, 205, 601 ActionDest: 152 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1096/fj.202000672R for your more information Rect: 93, 115, 224, 104 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.ejphar.2024.176550 for your more information Rect: 177, 70, 289, 59 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.ejphar.2024.176550 for your more information Rect: 45, 60, 88, 49 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/S0006-3495(97)78806-4 for your more information Rect: 416, 721, 549, 710 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/S0006-3495(97)78806-4 for your more information Rect: 306, 711, 334, 700 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1113/expphysiol.2009.050302 for your more information Rect: 363, 666, 525, 655 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1113/expphysiol.2010.056440 for your more information Rect: 321, 621, 484, 609 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.intimp.2015.08.007 for your more information Rect: 337, 566, 487, 554 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1159/000535753 for your more information Rect: 330, 511, 446, 499 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1055/s-0041-1740044 for your more information Rect: 497, 485, 549, 474 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1055/s-0041-1740044 for your more information Rect: 306, 475, 387, 464 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/bph.15685 for your more information Rect: 346, 420, 462, 409 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1159/000355835 for your more information Rect: 306, 385, 423, 374 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1096/fj.202101529R for your more information Rect: 358, 350, 488, 339 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.ejphar.2014.03.036 for your more information Rect: 488, 305, 549, 294 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.ejphar.2014.03.036 for your more information Rect: 306, 295, 392, 284 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.immuni.2024.03.023 for your more information Rect: 512, 260, 549, 249 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.immuni.2024.03.023 for your more information Rect: 306, 250, 424, 239 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.immuni.2024.04.018 for your more information Rect: 453, 215, 549, 203 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.immuni.2024.04.018 for your more information Rect: 306, 205, 368, 193 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/j.1365-2982.2004.00603.x for your more information Rect: 465, 160, 549, 148 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/j.1365-2982.2004.00603.x for your more information Rect: 306, 150, 389, 138 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1101/2023.07.13.548886 for your more information Rect: 451, 115, 549, 103 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1101/2023.07.13.548886 for your more information Rect: 306, 105, 350, 93 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.33549/physiolres.931865 for your more information Rect: 428, 70, 549, 58 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.33549/physiolres.931865 for your more information Rect: 306, 60, 330, 48 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.lfs.2012.03.031 for your more information Rect: 175, 721, 289, 710 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.lfs.2012.03.031 for your more information Rect: 45, 711, 67, 700 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/j.1464-410X.2006.05989.x for your more information Rect: 45, 666, 213, 655 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.autneu.2010.04.011 for your more information Rect: 160, 586, 289, 575 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.autneu.2010.04.011 for your more information Rect: 45, 576, 67, 565 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/j.1476-5381.1986.tb10206.x for your more information Rect: 186, 496, 289, 485 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1111/j.1476-5381.1986.tb10206.x for your more information Rect: 45, 486, 114, 475 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.neuint.2006.03.001 for your more information Rect: 132, 441, 282, 430 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.cell.2020.08.003 for your more information Rect: 190, 406, 289, 395 Annotation: Subtype: Link Contents: Please visit https://doi.org/10.1016/j.cell.2020.08.003 for your more information Rect: 45, 396, 86, 385 Annotation: Subtype: Link Contents: Please visit https://singlecell.broadinstitute.org/single_cell/study/SCP1038/the-human-and-mouse-enteric-nervous-system-at-single-cell-resolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=--&annotation=LABEL--group--cluster&subsample=100000 for your more information Rect: 81, 296, 289, 285 Annotation: Subtype: Link Contents: Please visit https://singlecell.broadinstitute.org/single_cell/study/SCP1038/the-human-and-mouse-enteric-nervous-system-at-single-cell-resolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=--&annotation=LABEL--group--cluster&subsample=100000 for your more information Rect: 45, 286, 289, 275 Annotation: Subtype: Link Contents: Please visit https://singlecell.broadinstitute.org/single_cell/study/SCP1038/the-human-and-mouse-enteric-nervous-system-at-single-cell-resolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=--&annotation=LABEL--group--cluster&subsample=100000 for your more information Rect: 45, 276, 289, 265 Annotation: Subtype: Link Contents: Please visit https://singlecell.broadinstitute.org/single_cell/study/SCP1038/the-human-and-mouse-enteric-nervous-system-at-single-cell-resolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=--&annotation=LABEL--group--cluster&subsample=100000 for your more information Rect: 45, 266, 289, 255 Annotation: Subtype: Link Contents: Please visit https://singlecell.broadinstitute.org/single_cell/study/SCP1038/the-human-and-mouse-enteric-nervous-system-at-single-cell-resolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=--&annotation=LABEL--group--cluster&subsample=100000 for your more information Rect: 45, 256, 289, 245 Annotation: Subtype: Link Contents: Please visit https://singlecell.broadinstitute.org/single_cell/study/SCP1038/the-human-and-mouse-enteric-nervous-system-at-single-cell-resolution?label=PEMN_1&genes=Avil%2CDclk1%2CChat%2CSlc5a7%2CSlc22a1%2CSlc22a2%2CSlc22a13%2CChrm3&cluster=mli.tsne2.txt&spatialGroups=--&annotation=LABEL--group--cluster&subsample=100000 for your more information Rect: 45, 246, 92, 235 Annotation: Subtype: Link Contents: E.Drokhlyansky, C. S.Smillie, N.Van Wittenberghe, etal., “The Human and Mouse Enteric Nervous System at SingleCell Resolution,” Cell182, no. 6 (2020): 1606 1622.e23, https://doi.org/10.1016/j.cell.2020.08.003. Rect: 99, 246, 107, 235 ActionDest: 181 Checksum: d7a523da Type: CRC32 Checksum: e061b8fb5e8af7272f3f1162ac5ded1d Type: MD5 Checksum: 8b975fde6e7a7dd2cc1b98d38c90a7148cfea826 Type: SHA-1 Checksum: 93f02b71fb6f6c0a92638dc43c5b3498cb4ce2fb0b73f7410869b25bc5bfe19b Type: SHA-256