Benzo(a)pyrene triggers desensitization of ?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 B(a)P can directly interact with the ?2ADR, we investigated here whether B(a)P could decrease ?2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a)P reduced ?2ADR-mediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP. Analysis of ?2ADR protein expression demonstrated that B(a)P rapidly decreased membrane expression of ?2ADR with a subsequent degradation of receptor protein. B(a)P exposure concomitantly rapidly increased the ?2ADR mRNA levels. The use of the ?-blockers, propranolol and ICI 118.551, demonstrated the involvement of ?2ADR itself in this increase. However, sustained exposure to B(a)P induced a diminution of ?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 ?2ADR. This may be taken in consideration when ?2-agonists/antagonists are administered in patients exposed to important concentrations of PAHs, e.g. in cigarette smokers.

SUBMITTER: Mayati A 

PROVIDER: S-EPMC5468268 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature