Membrane stabilizing, anti-oxidative interactions of propranolol and dexpropranolol with neutrophils

• Published in: Biochemical pharmacology 1996-07, Vol.52 (2), p.341-349
• Main Authors: Anderson, Ronald, Ramafi, Grace, Theron, Annette J.
• Format: Article
• Language: English
• Subjects: Acridines; Adenosine Triphosphate - metabolism; Antioxidants - pharmacology; Biological and medical sciences; Calcium - metabolism; Cell Membrane - drug effects; Cells, Cultured; dexpropranolol; Dose-Response Relationship, Drug; Humans; Luminescent Measurements; Lysophosphatidylcholines - metabolism; Medical sciences; membrane stabilization; Miscellaneous; Neutrophil Activation; neutrophils; Neutrophils - drug effects; Neutrophils - metabolism; oxidants; Pharmacology. Drug treatments; Platelet Activating Factor - metabolism; propranolol; Propranolol - pharmacology
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(96)00212-2

We have investigated the effects of the β-adrenoreceptor-blocking agent, propranolol (9–300 μM) on several pro-inflammatory activities of human neutrophils in vitro. Superoxide production by calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (9–18.7 μM) of this drug. However, inhibition of superoxide generation by neutrophils activated with phorbol myristate acetate (PMA), opsonized zymosan (OZ), and arachidonate (AA) only occurred with higher concentrations of propranolol, and coincided with decreased intracellular calcium fluxes, phospholipase A 2 (PLA 2) activity and synthesis of platelet-activating factor (PAF). Propranolol possessed neither cytotoxic nor superoxide-scavenging properties but, using a haemolytic assay of membrane-stabilizing activity, this agent neutralized the membrane-disruptive effects of the bioactive phospholipids, lysophosphatidylcholine (LPC), PAF, and lysoPAF (LPAF). A mechanistic relationship between the anti-oxidative and membrane-stabilizing properties of propranolol was suggested by the observation that pretreatment of neutrophils with LPC or PAF eliminated the inhibitory effects of the drug on superoxide generation by PMA-activated neutrophils. Dexpropranolol, a stereoisomer with minimal β-blocking activity, and propranolol were equally effective with respect to their membrane-stabilizing and anti-oxidative interactions with neutrophils, but several other β-blocking agents (atenolol, metoprolol, sotalol, and timolol) did not possess these activities. Inhibition of oxidant generation is, therefore, not a common property of β-blocking agents and, in the case of propranolol, appears to occur as a consequence of membrane-stabilization rather than by β-receptor-directed effects.