Differential sensitivity of mussel tissues to pharmaceutical exposures: Putative relationship with specific pathways of interaction

Propranolol is a beta-adrenergic receptor-blocker widely used in cardiovascular diseases therapies, and detected in aquatic systems at concentrations up to 56 ng/L. Due to similarities between human and other vertebrate beta-adrenergic receptors, consequences of beta-blocker exposure in vertebrate wildlife, such as fish may be expected. Instead, little is known about the presence and function of these receptors in invertebrates, and possible effects of beta-blockers are then unpredictable. In a preliminary study [Fabbri et al. (2009) Comp. Biochem. Physiol 154A:S15] we showed that mussel exposure to 0.3 and 30 μg/L of (−)-propranolol caused a stress syndrome and alteration of cell signaling. Here we assessed whether propranolol in the chemical form and concentrations encountered in coastal environments induces detectable responses in mussels. Mussels (Mytilus galloprovinicialis) were exposed for 7 days to five concentrations of (±)-propranolol, namely 0.3, 3, 30, 300, 30,000 ng/L; the three lowest concentrations represented the environmental range. Different endpoints related to the beta-adrenergic pathway and to the stress response were evaluated in digestive gland and mantle, as the tissues showing the highest responsiveness in preliminary trials. Both cAMP levels and PKA activity were reduced in digestive gland, while increased in mantle. Similar expression patterns were observed for the MXR-related genes, a suite of transporters involved in xenobiotic metabolism. The opposite responses of the tissues may result from differently expressed receptor types, suggesting the occurrence of different interaction pathways. Significant effects were observed at concentrations as low as 0.3 ng/L, indicating that (±)-propranolol at environmental levels affects physiological pathways in mussels.