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Neural targets of the enteric dopaminergic system in regulating motility of rat proximal colon

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Abstract

In isolated segments of the rat proximal colon, the dopamine reuptake inhibitor GBR 12909 (GBR) causes a dilatation, while the D1-like receptor antagonist SCH 23390 (SCH) induces a tonic constriction, suggesting that neurally released dopamine tonically stimulates enteric inhibitory efferent neurons. Here, the targets of the enteric dopaminergic neurons were investigated. Cannulated segments of rat proximal colon were bathed in physiological salt solution and luminally perfused with 0.9% saline, while all drugs were applied to the bath. Spatio-temporal maps of colonic motility were constructed from video recordings of peristaltic contractions, and the maximum diameter was measured as an index of colonic contractility. GBR (1 μM)-induced dilatations of colonic segments were prevented by SCH (5 μM), L-nitro arginine (L-NA; 100 μM), a nitric oxide synthase inhibitor, or tetrodotoxin (0.6 μM). In contrast, constrictions induced by a higher concentration of SCH (20 μM) were unaffected by either L-NA or tetrodotoxin. The vasoactive intestinal peptide (VIP) receptor antagonist VIP10-28 (3 μM) or P2Y1 receptor antagonist MRS 2500 (1 μM) had no effect on either the GBR-induced dilatation or the SCH-induced constriction. In colonic segments that had been pretreated with 6-hydroxydopamine (100 μM, 3 h) to deplete enteric dopamine, GBR failed to increase the colonic diameter, while SCH was still capable of constricting colonic segments. Enteric dopaminergic neurons appear to project to nitrergic neurons to dilate the proximal colon by activating neuronal D1-like receptors. In addition, constitutively activated D1-like receptors expressed in cells yet to be determined may provide a tonic inhibition on colonic constrictions.

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Data availability

Data is available on demand from Dr. Hiroyuki Nakamori in whose laboratory this research was undertaken.

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Acknowledgements

The authors thank Dr Richard Lang (Monash University) for critically reading the manuscript.

Funding

The present study was supported by a research grant from the Nitto Foundation and Grant-in-Aid for Young Scientists (JP20K16964) from Japan Society for the Promotion of Science (JSPS) to HN.

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Authors and Affiliations

  1. Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan

    Hiroyuki Nakamori & Hikaru Hashitani

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HN and HH were responsible for the conception and design of the experiments. HN was responsible for the collection, analysis, and interpretation of data. HN and HH were responsible for drafting the article or revising it critically for important intellectual content. HN and HH have read and approved the final manuscript submitted for publication and are accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify are listed.

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Correspondence to Hiroyuki Nakamori.

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The experimental procedures were performed according to the guidelines for the care and use of laboratory animals approved by the Experimental Animal Committee of the Nagoya City University Graduate School of Medical Sciences (Approval no: H30M-27).

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Nakamori, H., Hashitani, H. Neural targets of the enteric dopaminergic system in regulating motility of rat proximal colon. Pflugers Arch - Eur J Physiol 475, 1315–1327 (2023). https://doi.org/10.1007/s00424-023-02849-1

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