title: Venlafaxine and atenolol disrupt epinephrine-stimulated glucose production in rainbow trout hepatocytes.
abstract: The beta-blocker atenolol (ATEN), and the selective serotonin and norepinephrine reuptake inhibitor, venlafaxine (VEN) are found in municipal wastewater effluents, but little is known about the effect of these pharmaceuticals on aquatic animals. We tested the hypothesis that VEN and ATEN disrupt acute stress mediated glucose production in fish liver. To this end, rainbow trout (Oncorhynchus mykiss) hepatocytes were exposed in vitro to different concentrations (0, 0.1, 10, 1000 nM) of VEN or ATEN and glucose production in response to either cortisol or epinephrine (two key stress hormones) was ascertained. Both VEN and ATEN did not affect either the unstimulated or cortisol (100 ng/mL)-stimulated glucose release over a 24 h period. The acute (3 h) unstimulated glucose production by isolated hepatocytes in suspension was also not modified by ATEN, while VEN (100 and 1000 nM) reduced basal glucose release. However, ATEN, even at concentration as low as 0.01 nM completely abolished epinephrine (1 μM)-induced glucose production in trout hepatocytes. Interestingly, VEN also suppressed epinephrine-induced glucose production but only at higher concentrations (100 and 1000 nM). Neither VEN nor ATEN significantly impacted the glucose production in response to either 8-bromo-cAMP (cAMP analogue) or glucagon (a metabolic hormone that increases glucose production) stimulation. ATEN but not VEN attenuated the epinephrine-induced increase in glucose transporter 2 (GLUT2) mRNA abundance in trout hepatocytes. Taken together, our results suggest that the impact of ATEN and VEN on glucose production involves inhibition of β-adrenoceptor signaling in trout hepatocytes. Overall, VEN and ATEN are beta-blockers and may disrupt the adaptive acute glucose response to a secondary stressor in rainbow trout.
authors: Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors: J S
authors: JS
authors: Ings
authors: N
authors: N
authors: George
authors: M C S
authors: MC
authors: Peter
authors: M R
authors: MR
authors: Servos
authors: M M
authors: MM
authors: Vijayan
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000633:toxicity; D000818:Animals; D001262:Atenolol / Q000633:toxicity*; D003511:Cyclohexanols / Q000633:toxicity*; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology; D017686:Oncorhynchus mykiss / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity; D000069470:Venlafaxine Hydrochloride; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001262:Atenolol; D003511:Cyclohexanols; D004837:Epinephrine; D005947:Glucose; D006854:Hydrocortisone; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; D014874:Water Pollutants, Chemical