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Basal release of 6-cyanodopamine from rat isolated vas deferens and its role on the tissue contractility

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Abstract

6-Cyanodopamine is a novel catecholamine released from rabbit isolated heart. However, it is not known whether this catecholamine presents any biological activity. Here, it was evaluated whether 6-cyanodopamine (6-CYD) is released from rat vas deferens and its effect on this tissue contractility. Basal release of 6-CYD, 6-nitrodopamine (6-ND), 6-bromodopamine, 6-nitrodopa, and 6-nitroadrenaline from vas deferens were quantified by LC-MS/MS. Electric-field stimulation (EFS) and concentration-response curves to noradrenaline, adrenaline, and dopamine of the rat isolated epididymal vas deferens (RIEVD) were performed in the absence and presence of 6-CYD and /or 6-ND. Expression of tyrosine hydroxylase was assessed by immunohistochemistry. The rat isolated vas deferens released significant amounts of both 6-CYD and 6-ND. The voltage-gated sodium channel blocker tetrodotoxin had no effect on the release of 6-CYD, but it virtually abolished 6-ND release. 6-CYD alone exhibited a negligible RIEVD contractile activity; however, at 10 nM, 6-CYD significantly potentiated the noradrenaline- and EFS-induced RIEVD contractions, whereas at 10 and 100 nM, it also significantly potentiated the adrenaline- and dopamine-induced contractions. The potentiation of noradrenaline- and adrenaline-induced contractions by 6-CYD was unaffected by tetrodotoxin. Co-incubation of 6-CYD (100 pM) with 6-ND (10 pM) caused a significant leftward shift and increased the maximal contractile responses to noradrenaline, even in the presence of tetrodotoxin. Immunohistochemistry revealed the presence of tyrosine hydroxylase in both epithelial cell cytoplasm of the mucosae and nerve fibers of RIEVD. The identification of epithelium-derived 6-CYD and its remarkable synergism with catecholamines indicate that epithelial cells may regulate vas deferens smooth muscle contractility.

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Acknowledgments

Sao Paulo Research Foundation (FAPESP) grants 2021/14414-8 (JBJ), 2017/15175-1 (EA); 2019/16805-4 (GDN).

National Council for Scientific and Technological Development (CNPq) grant 303839/2019-8 (GDN).

Funding

Coordination for the Improvement of Higher Education Personnel (CAPES) grant 001(CFSDP). Sao Paulo Research Foundation (FAPESP) grants 2021/14414-8 (JBJ), 2022/13062-3 (JFAB), 2021/13726-6 (VBS), 2017/15175-1 (EA); 2019/16805-4 (GDN).

National Council for Scientific and Technological Development (CNPq) grant 303839/2019-8 (GDN)

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  1. Caroline Fernanda Sanches Dal Pozzo and Jose Eduardo Maldonado Junior contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil

    Caroline Fernanda Sanches Dal Pozzo, José Britto-Júnior, João Felipe Agostini Badin, Valéria Barbosa de Souza, André Almeida Schenka, Edson Antunes & Gilberto De Nucci

  2. Department of Surgery, Faculty of Medicine of Jundiaí, Jundiaí, Brazil

    Jose Eduardo Maldonado Junior & Adriano Fregonesi

  3. Department of Chemistry, Rhodes College, Memphis, Tennessee, USA

    Larryn W. Peterson

  4. Division of Urology, Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil

    Adriano Fregonesi

  5. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil

    Gilberto De Nucci

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Contributions

Conceptualization: JBJ, GDN. Data curation: JBJ, GDN. Formal analysis: GDN. Funding acquisition: EA, GDN. Investigation: CFSDP, JEMJ, JBJ, JFAB, VBZ, AAD. Methodology: CFSDP, JBJ, GDN. Project administration: GDN, JBJ. Supervision: EA and GDN. Visualization: AF,LWP, EA, GDN. Writing – original draft: JBJ, GDN.

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Correspondence to José Britto-Júnior.

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Pozzo, C.F.S.D., Junior, J.E.M., Britto-Júnior, J. et al. Basal release of 6-cyanodopamine from rat isolated vas deferens and its role on the tissue contractility. Pflugers Arch - Eur J Physiol (2024). https://doi.org/10.1007/s00424-024-02985-2

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