Herbicide acetochlor inhibits adrenergic receptor-mediated calcium oscillations in rat hepatocytes

Herbicide acetochlor after application enters both surface and underground waters, so that acetochlor concentrations in rivers and streams could be sufficiently high (nmol·L⁻¹) to exert long-term effects in aquatic animals．Occupational exposure may pose greater risks due to skin and inhalation exposures, resulting in much higher transient blood acetochlor concentrations (μmol·L⁻¹)．Previous works have identified liver as the most susceptible toxicological target for acetochlor, and cytosolic calcium is known to play a vital role in multiple hepatocyte functions．Therefore the present work aims to examine acetochlor effect on calcium oscillations induced by adrenergic receptor activation in freshly isolated rat hepatocytes. It was found that acetochlor at lower concentrations (1, 10 μmol·L⁻¹) added simultaneously with phenylepinephrine (PE) had no effect on PE-induced calcium oscillations, but inhibited reversibly calcium oscillations at higher doses (50, 100, 200 μmol·L⁻¹) of acetochlor in selected hepatocytes．Brief prior acetochlor exposure (1, 10, 100 μmol·L⁻¹), however, had no apparent effect on either basal calcium or subsequent PE-induced calcium oscillations．Immunocytochemistry identified non-uniform α1 adrenergic receptor expression among isolated hepatocytes．Immunohistochemistry of liver slices revealed a distinct pattern of α1 adrenergic receptor density in liver lobules: a gradual low-to-high receptor density gradient from pericentral to periportal regions．This receptor density gradient is likely related to acetochlor inhibition in selected hepatocytes．Taken together it is concluded that acetochlor at blood concentrations attainable during acute skin exposure or acetochlor poisoning may exert transient inhibitory effects on α1 receptor signaling in the liver．