Benzo(a) pyrene triggers desensitization of beta 2-adrenergic pathway

Abstract : Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a) pyrene (B(a) P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that Ba) P can directly interact with the beta 2ADR, we investigated here whether B(a) P could decrease beta 2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a) P reduced beta 2ADRmediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP. Analysis of beta 2ADR protein expression demonstrated that B(a) P rapidly decreased membrane expression of beta 2ADR with a subsequent degradation of receptor protein. B(a) P exposure concomitantly rapidly increased the beta 2ADR mRNA levels. The use of the beta-blockers, propranolol and ICI 118.551, demonstrated the involvement of beta 2ADR itself in this increase. However, sustained exposure to Ba) P induced a diminution of beta 2ADR mRNA steady-state as a result of the acceleration of its degradation. Together, these results show that, beside the well-known activation of the aryl hydrocarbon receptor, PAH deleterious effects may involve the dysfunction of adrenergic responses through, in part, the desensitization of beta 2ADR. This may be taken in consideration when beta 2-agonists/antagonists are administered in patients exposed to important concentrations of PAHs, e.g. in cigarette smokers.
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Abdullah Mayati, Normand Podechard, Manuelle Rineau, Lydie Sparfel, Dominique Lagadic-Gossmann, et al.. Benzo(a) pyrene triggers desensitization of beta 2-adrenergic pathway. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.3262 ⟨10.1038/s41598-017-03646-4⟩. ⟨hal-01560151⟩



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