Acetylcholine and adenosine triphosphate (ATP) raise intracellular Ca2+ concentration via muscarinic receptors and P2U purinoceptors by releasing Ca2+ from intracellular Ca2+ stores in the neural retina of early embryonic chick. The signal transduction mechanisms for the muscarinic and purinergic Ca2+ responses were studied with fura-2 fluorescence measurements. Li+ (1 mM), which inhibits phosphatidylinositol metabolism, enhanced both the Ca2+ rises to carbamylcholine (CCh. 30 microM) a muscarinic agonist and ATP (200 microM). Thapsigargin (250 nM), an inhibitor of Ca(2+)-ATPase of inositol trisphosphate (IP3)-sensitive Ca2+ stores, abolished both the Ca2+ rises to CCh (100 microM) and ATP (500 microM). U-73122 (2 microM), an inhibitor of phospholipase C beta, suppressed the Ca2+ rise to ATP (500 microM), but its analog U-73343 (2 microM) did not suppress it. In contrast, both U-73122 and U-73343 suppressed the Ca2+ the Ca2+ rise to CCh (100 microM). Pertussis toxin (250 ng/ml) suppressed the ATP-induced Ca2+ rise at least partly, whereas no inhibition was observed on the CCh-induced Ca2+ rise. Cross-talk occurred between the muscarinic and purinergic Ca2+ mobilizations but they were not occlusive. This study suggests that the muscarinic and purinergic Ca2+ mobilizations utilize IP3-sensitive Ca2+, stores, but different signal transduction pathways are involved in between the muscarinic and purinergic Ca2+ responses.