Research paperSelective lysosomal uptake and accumulation of the beta-adrenergic antagonist propranolol in cultured and isolated cell systems
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2022, Journal of Affective DisordersCitation Excerpt :Several studies have shown that methylation of certain sites within serotonin pathway genes such as the serotonin transporter gene (SLC6A4), tryptophan hydroxylase 2 gene (TPH2), and serotonin receptor gene (HTR1A, HTR1B) was connected to the outcomes of the antidepressant treatment (Gasso et al., 2017; Schiele et al., 2021; Shen et al., 2020; Wang et al., 2018). Nowadays, most clinical antidepressant drugs are based on the “monoamine hypothesis”, which may regulate the levels of monoamine transmitters (e.g., serotonin, dopamine, and norepinephrine) between synapses to achieve the antidepressant effect (Cramb, 1986). The 5-HT1A and 5-HT1B receptors, present both pre- and post-synaptically, are broadly distributed in the central nervous system, and their function can influence the activity of serotonergic neurons (Mekli et al., 2011).
Cytotoxicity of binary mixtures of human pharmaceuticals in a fish cell line: Approaches for non-monotonic concentration-response relationships
2014, ChemosphereCitation Excerpt :To investigate whether differences in lysosomal number or structure were apparent, pharmaceutical-exposed cells were examined microscopically after incubation in the presence of neutral red (Fig. 1). In the case of PPN, the appearance of large, swollen lysosomes probably indicates direct lysosomal uptake and accumulation of PPN, which has been reported previously for this compound (Cramb, 1986). A degree of lysosomal swelling was also visible in cells treated with FL, although the degree of uptake appeared to be marked less than that observed for PPN.
A live-cell fluorescence microplate assay suitable for monitoring vacuolation arising from drug or toxic agent treatment
2010, Journal of Biomolecular ScreeningCitation Excerpt :Two of these agents, propranolol and GF-109203X, have previously been reported to induce phospholipidosis in cells. Propranolol is a well-known and extensively investigated cationic amphiphilic drug that induces phospholipidosis.17,19 High micromolar concentrations of the drug are rapidly taken up and accumulated by a wide range of cultured cells, with a steady state being reached after 40- to 60-min administration and half-maximum uptake within 4 to 10 min.
Contribution of lysosomes to concentrative uptake of DX-9065a into rat liver
2006, Journal of Pharmaceutical SciencesCitation Excerpt :After a single intravenous administration of [14C]-DX-9065a to rats, the radioactivity in the liver continuously increased up to 6 h and showed a Kp value of 90.5, representing concentrative uptake against the radioactivity concentration gradient between liver and plasma. To account for the concentrative uptake phenomena of cationic organic compounds in certain tissues, some mechanisms have been proposed in the literature, and they can be categorized into two types: (A) binding to intracellular components of phosphatidylserine,23,24 lysosomes,22,25–29 and mitochondria;21 and (B) uptake by a carrier protein17,30 or a receptor-mediated endocytosis system.18,31 In many cases, however, the contribution of each mechanism was evaluated solely, and it is, therefore, still unclear which mechanism predominantly accounts for the concentrative distribution profile of the corresponding drug.
α-Tocopherol influences the lipid membrane affinity of desipramine in a pH-dependent manner
2004, European Journal of Pharmaceutical SciencesAntioxidant and lysosomotropic properties of acridine-propranolol: Protection against oxidative endothelial cell injury
2002, Journal of Molecular and Cellular Cardiology