ETHANOL PERTURBS RECEPTOR-OPERATED CYTOSOLIC-FREE CALCIUM-CONCENTRATION SIGNALS IN CULTURED RAT HEPATOCYTES

Background & Aims: Studies of the acute effects of ethanol on hepatoce llular free calcium concentration, [Ca2+](i), and on receptor-operated [Ca2+](i) signals have produced conflicting results, The effects of e thanol on basal and receptor-operated [Ca2+](i) signals in rat hepatoc ytes cultured on two different extracellular matrices were examined, M ethods: [Ca2+](i) was determined by digitized fluorescence microscopy and inositol 1,4,5-trisphosphate (Ins[1,4,5]P-3) by high-performance l iquid chromatography (HPLC). Results: Ethanol induced an increase in [ Ca2+](i) in hepatocytes cultured on collagen I but not on the more phy siological substratum, matrigel, Compared with hepatocytes cultured on matrigel, cells on collagen I exerted less responsiveness and lower a mplitude of [Ca2+](i) signals to vasopressin or phenylephrine, The eff ects of ethanol on receptor-operated [Ca2+](i) signals were examined i n hepatocytes cultured on matrigel, Incubation of hepatocytes with phy siologically attainable concentrations of ethanol (20-30 mmol/L) for 3 0 minutes to 48 hours perturbed epidermal growth factor, phenylephrine , and lower concentration (less than or equal to 1 nmol/L) of vasopres sin-induced [Ca2+](i) signaling by reducing the amplitude and changing the pattern of [Ca2+](i) signals, Alcohol induced-impairment of [Ca2](i) signaling was associated with decreased production of Ins(1,4,5)P -3. Conclusions: Alcohol does not itself evoke an increase in [Ca2+](i ) in hepatocytes cultured on matrigel but perturbs receptor-operated [ Ca2+](i) signaling. This is associated with and could be caused by imp aired generation of Ins(1,4,5)P-3.