Dobutamine inhibits vasopressin-mediated water transport across toad bladder epithelium

Franco, Wilson; Leite, Renner de Souza

doi:10.1016/j.cbpc.2008.03.008

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…To our surprise, the dobutamine-induced proliferation could not be antagonized by metoprolol or propranolol. Even though dobutamine has previously been shown to also act as a a 2 -adrenoceptor agonist at high concentrations (Franco & Leite Rde, 2008), we ran pilot experiments with the a-adrenoceptor agonist phenylephrine which showed no proliferative effect even at concentrations up to 10 mM. Atypical b 1 -adrenoceptors, that is, not pharmacologically resembling the b 1-3 -adrenoceptors, have been identified in cell cultures of murine brown adipocytes, the murine heart, the rat aorta and in the human pulmonary artery (Shafiei & Mahmoudian, 1999;Kaumann et al, 2001;Jost et al, 2002;Kozlowska et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Proliferation of the human urothelium is induced by atypical β₁‐adrenoceptors

Winder

Wasén

Aronsson

et al. 2015

Auton Autocoid Pharmacol

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We wanted to assess whether β-adrenoceptors mediate proliferation in the normal and malignant urothelial cell lines UROtsa and T24, respectively. Urothelial cells were cultured for 24 h in the presence of the β-adrenoceptor agonists isoprenaline (β1/2/3 ), dobutamine (β1 ), salbutamol (β2 ), BRL 37344 (β3 ), CGP 12177 (a partial β-agonist) or β-adrenoceptor antagonists (metoprolol; β1 , propranolol; β1/2 ). Phosphorylation of kinases was screened with a Human Phospho-Kinase Array Kit (R&D systems). Intracellular pathways activated by proliferation of urothelial cells were characterized by incubating cells with the MEK1/2 inhibitor PD 98,059, the p38 kinase inhibitor losmapimod or with the Akt 1/2 kinase inhibitor. Proliferation was assessed with the MTT proliferation assay (ATCC). Western blot and immunocytochemistry were used for detection of the β1 -adrenoceptor. Isoprenaline and dobutamine induced proliferation, while salbutamol and BRL 37344 did not. Dobutamine-induced proliferation was not affected by metoprolol or propranolol but was instead antagonized by CGP 12177 in T24 but not in UROtsa. In response to stimulation with dobutamine, Akt1/2/3 was phosphorylated in UROtsa, while ERK1/2 and p38 were phosphorylated in T24. MEK1/2 inhibition blocked basal and dobutamine-induced proliferation in T24 but only basal proliferation in UROtsa. Losmapimod slightly inhibited basal proliferation in T24 but not dobutamine-induced proliferation. Akt 1/2 inhibitor blocked basal and dobutamine-induced proliferation in UROtsa. Immunocytochemistry and Western blot revealed expression of β1 -adrenoceptors in both urothelial cell lines. The present data show that the urothelium expresses atypical β1-adrenoceptors that activate intracellular kinases inducing urothelial proliferation.

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Section: Discussionmentioning

confidence: 99%