Ruthenium red inhibits cytosolic Ca2+ oscillations induced by vasopressin in primary cultured hepatocytes.

The effects of ruthenium red were investigated on the vasopressin (Vp)-induced Ca2+ response in single, primary cultured rat hepatocytes loaded with fura-2. Low concentrations of Vp (1 nM) evoked a sustained train of baseline spike Ca2+ oscillations, with a latency to first peak of 170 s and a frequency of 0.37 min(-1). Treatment of hepatocytes with a higher concentration of Vp (10 nM) resulted in a rapid rise in intracellular Ca2+, with less delay (40 s), and which remained elevated and sustained. Microinjection of a low concentration of ruthenium red (10 microM in the injection pipette) altered the observed response to 1 nM Vp such that only 2 - 4 base line spikes were observed. A higher concentration of ruthenium red (50 microM in the injection pipette) completely abolished the 1 nM Vp response. However, the Ca2+ responses to higher concentrations of Vp (10 nM) or to the Ca2+-ATPase inhibitor, thapsigargin, were unaffected by ruthenium red. These results show that low concentrations of ruthenium red inhibit the Vp-induced oscillatory Ca2+ response and suggest a contribution of a ryanodine receptor-mediated Ca2+-induced Ca2+ release in generating the baseline spike oscillations in rat hepatocytes.