The role of prostaglandin F-2 alpha (PGF(2 alpha)) interaction with arginine vasopressin (AVP) in modulating intracellular Ca2+ homeostasis was studied. Examinations were done on single cultured mesangial cells loaded with fura-2. Pretreatment of cultured mesangial cells during 1 min with different concentrations of PGF(2 alpha) (10(-5)-10(-8) M) caused a significant prolongation of [Ca2+](i) transients after subsequent AVP applications. The observed effect of a prolonged sustained phase was not influenced by the temporal sequence of AVP stimulation after preincubation with PGF(2 alpha): the signal was modulated in nearly the same way after 5 min delay as after nearly simultaneous application of AVP and PGF(2 alpha). Measurements in Ca2+-free medium showed that the prolonged sustained phase of [Ca2+](i) transients after AVP applications in cells pretreated with PGF(2 alpha), was mostly due to Ca2+ release from intracellular store(s). Pretreatment of the cells with PGF(2 alpha) also greatly enhanced the % of AVP responsive cells. Even at concentrations of AVP as low as 10(-10) M about 30% of cells pretreated with PGF(2 alpha) responded with the fast [Ca2+](i) rise. Thus, present studies showed that PGF(2 alpha) specifically modulates [Ca2+](i) transients after AVP stimulation and enhances sensitivity of mesangial cells to AVP. The results help to identify PGF(2 alpha) participation in the cellular regulatory mechanisms of microcirculation and filtration in the kidney.