We have previously reported that extracellular ATP causes a transient rise in intracellular calcium concentration ([Ca2+](i)) in cultured Schwann cells derived from adult animal [Ansselin A. D. et al. (1994) Int. J. Neurosci. 74, 148]. In the study, the receptor mediating this response has been characterized. Established adult rat and rabbit Schwann cell cultures were located with fura-2 (acetoxy-methyl ester, 10 mu mol/l. 40 min, 37 degrees C), which indicated, by fluorescence imaging, a resting [Ca2+](i) of 34.7 +/- 1.4 nmol/l (mean +/- S.E., n=591). The cells were exposed to 100 mu mol/l ATP, ADP, AMP, UTP and adenosine in defined medium for 1-2 min, and the change in [Ca2+](i) was observed as a change in the Fura-2 ratio. Seventy-seven percent of adult rat Schwann cells (n=235) and 88% adult rabbit Schwann cells (n=356) responded to the presence of extracellular ATP (100 mmol/l) with a transient increase in [Ca2+](i) (41 and 90 nmol/l from resting value, respectively), independent of the presence of [Ca2+](o). Calcium waves were observed in one experiment. The following order of agonist potency was observed: UTP=ATP much greater than ADP>AMP=adenosine. The agonists alpha,beta-methylene-ATP and 2-methylthio-ATP had a small effect on the cells, similar to AMP, and were mutually desensitizing. The ATP antagonist suramin blocked the response. We conclude that adult Schwann cells express a purinergic ATP receptor belonging to the G-protein-coupled P-2u subtype [O'Connor S. et. al. (1991) Trends pharmac. Sci. 12, 137-141]. Copyright (C) 1996 IBRO.