PMID- 33297453 OWN - NLM STAT- MEDLINE DCOM- 20210708 LR - 20210708 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 9 IP - 12 DP - 2020 Dec 7 TI - Effect of Beta 3 Adrenoreceptor Modulation on Patency of the Ductus Arteriosus. LID - 10.3390/cells9122625 [doi] LID - 2625 AB - beta3-adrenoreceptor (beta3-AR), a G-protein coupled receptor, has peculiar regulatory properties in response to oxygen and widespread localization. beta3-AR is expressed in the most frequent neoplasms, also occurring in pregnant women, and its blockade reduces tumor growth, indicating beta3-AR-blockers as a promising alternative to antineoplastic drugs during pregnancy. However, beta3-AR involvement in prenatal morphogenesis and the consequences of its blockade for the fetus remain unknown. In this study, after the demonstrated expression of beta3-AR in endothelial and smooth muscle cells of ductus arteriosus (DA), C57BL/6 pregnant mice were acutely treated at 18.5 of gestational day (GD) with indomethacin or with the selective beta3-AR antagonist SR59230A, or chronically exposed to SR59230A from 15.5 to 18.5 GD. Six hours after the last treatment, fetuses were collected. Furthermore, newborn mice were treated straight after birth with BRL37344, a beta3-AR agonist, and sacrificed after 7 h. SR59230A, at the doses demonstrated effective in reducing cancer progression (10 and 20 mg/kg) in acute and chronic mode, did not induce fetal DA constriction and did not impair the DA ability to close after birth, whereas at the highest dose (40 mg/kg), it was shown to cause DA constriction and preterm-delivery. BRL37344 administered immediately after birth did not alter the physiological DA closure. FAU - Pini, Alessandro AU - Pini A AUID- ORCID: 0000-0001-9828-2082 AD - Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy. FAU - Fazi, Camilla AU - Fazi C AD - Department of Health Sciences, University of Florence, 50139 Florence, Italy. FAU - Nardini, Patrizia AU - Nardini P AUID- ORCID: 0000-0003-2374-5147 AD - Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy. FAU - Calvani, Maura AU - Calvani M AUID- ORCID: 0000-0003-0750-4706 AD - Department of Paediatric Haematology-Oncology, A. Meyer University Children's Hospital, 50139 Florence, Italy. FAU - Fabbri, Sergio AU - Fabbri S AD - Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy. FAU - Guerrini, Alessandro AU - Guerrini A AUID- ORCID: 0000-0002-8224-4919 AD - Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano dell'Emilia, Italy. FAU - Forni, Giulia AU - Forni G AD - Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pediatric Neurosciences, "A. Meyer" University Children's Hospital, 50139 Florence, Italy. FAU - La Marca, Giancarlo AU - La Marca G AD - Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pediatric Neurosciences, "A. Meyer" University Children's Hospital, 50139 Florence, Italy. FAU - Rosa, Arianna Carolina AU - Rosa AC AUID- ORCID: 0000-0002-6139-9241 AD - Department of Scienza e Tecnologia del Farmaco, University of Turin, 10125 Turin, Italy. FAU - Filippi, Luca AU - Filippi L AD - Division of Neonatology and NICU, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201207 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate) RN - 0 (Adrenergic beta-3 Receptor Antagonists) RN - 0 (Ethanolamines) RN - 0 (Propanolamines) RN - 0 (Receptors, Adrenergic, beta-3) RN - 0 (Receptors, G-Protein-Coupled) RN - 5DZZ1926YW (BRL 37344) RN - XXE1CET956 (Indomethacin) SB - IM MH - Adrenergic beta-3 Receptor Antagonists/*pharmacology MH - Animals MH - Animals, Newborn MH - Disease Models, Animal MH - Disease Progression MH - Ductus Arteriosus/drug effects/*metabolism MH - Ductus Arteriosus, Patent/drug therapy/*metabolism MH - Ethanolamines/pharmacology MH - Female MH - Indomethacin/pharmacology MH - Male MH - Maternal Exposure MH - Mice MH - Mice, Inbred C57BL MH - Pregnancy MH - Pregnancy, Animal MH - Propanolamines/pharmacology MH - Receptors, Adrenergic, beta-3/*metabolism MH - Receptors, G-Protein-Coupled/metabolism MH - Time Factors PMC - PMC7762377 OTO - NOTNLM OT - cancer OT - ductus arteriosus OT - pregnancy OT - beta3-adrenorceptor COIS- The authors declare no conflict of interest. EDAT- 2020/12/11 06:00 MHDA- 2021/07/09 06:00 PMCR- 2020/12/07 CRDT- 2020/12/10 01:03 PHST- 2020/10/30 00:00 [received] PHST- 2020/12/02 00:00 [revised] PHST- 2020/12/06 00:00 [accepted] PHST- 2020/12/10 01:03 [entrez] PHST- 2020/12/11 06:00 [pubmed] PHST- 2021/07/09 06:00 [medline] PHST- 2020/12/07 00:00 [pmc-release] AID - cells9122625 [pii] AID - cells-09-02625 [pii] AID - 10.3390/cells9122625 [doi] PST - epublish SO - Cells. 2020 Dec 7;9(12):2625. doi: 10.3390/cells9122625.