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β1- and β12-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens

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Abstract

6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective β-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective β1- and β12-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective β1-adrenergic receptor antagonists atenolol (0.1 and 1 µM), betaxolol (1 µM), and metoprolol (1 µM) and the unselective β12-adrenergic receptor antagonists propranolol (1 and 10 µM) and pindolol (10 µM) caused significant rightward shifts of the concentration–response curve to 6-ND (pA2 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective β1- and β12-adrenergic receptor antagonists at a higher concentration (atenolol 1 µM, betaxolol 1 µM, metoprolol 1 µM, propranolol 10 µM, and pindolol 10 µM) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective β1-adrenoceptor agonist RO-363, the selective β2-adrenoceptor agonist salbutamol, and the selective β3-adrenoceptor agonist mirabegron, up to 300 µM, had no effect on the RIEVD tone. The results demonstrate that β1- and β1-/β2-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.

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The authors authorize the availability of any data used in this study.

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Funding

ATL thanks FAPESP for PhD fellowship (2021/13593–6).

ACA thanks CAPES for master’s fellowship (001).

JBJ thanks CAPES for PhD fellowship (001).

RRC thanks FAPESP for scientific initiation fellowship (2021/14120–4).

EA and FM thank FAPESP (2017/15175–1).

GDN thanks FAPESP (2019/16805–4) and CNPq (303,839/2019–8).

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Authors and Affiliations

Authors

Contributions

Conceptualization: JBJ, GDN.

Data curation: JBJ, GDN.

Formal analysis: GDN.

Funding acquisition: EA, GDN.

Investigation: ATL, ACA, JBJ, RRC, GDN.

Methodology: ATL, ACA, JBJ, RRC, AF, EA, FZM, GDN.

Project administration: GDN.

Supervision: FZM, EA.

Visualization: AF, EA, GDN.

Writing—original draft: JBJ, AF, EA, GDN.

The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to José Britto-Júnior.

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Ethics approval

All experimental protocols were authorized by the Ethics Committee in Animal Use of UNICAMP (CEUA/UNICAMP, protocol numbers 5952–1/2022 and 5831–1/2021).

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Not applicable.

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The authors authorize the submission and publication of this article in Naunyn–Schmiedeberg’s Archives of Pharmacology.

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The authors declare no competing interests.

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Lima, A.T., Amorim, A.C., Britto-Júnior, J. et al. β1- and β12-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 395, 1257–1268 (2022). https://doi.org/10.1007/s00210-022-02268-6

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  • DOI: https://doi.org/10.1007/s00210-022-02268-6

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