Treatment of NCB-20 neuronal hybrid cells in culture with 100 microM ATP, 100 microM carbachol or 1 microM bradykinin is followed by a transient rise in intracellular calcium ion concentration ([Ca2+]i). Exposure of these cells to any one of these three agonists (ATP, carbachol or bradykinin) is also followed by heterologous desensitization of responses mediated by either of the other two classes of agonist. The heterologous desensitization is not inhibited by Ro-31-2880 (a selective protein kinase C inhibitor), neither is it accompanied by a reduction in the receptor-dependent increase in inositol trisphosphate. Cells were pre-treated in the absence or presence of extracellular Ca2+ with 1 microM bradykinin, 100 microM carbachol or carrier alone, and thereafter exposed to 1 microM ionomycin. The results showed that pre-treatment with bradykinin or carbachol reduced the maximum increase in [Ca2+]i triggered by ionomycin. Exposure of cells to 1 microM ionomycin in the absence of extracellular Ca2+ totally eliminated the subsequent increase in [Ca2+]i mediated by bradykinin, ATP or carbachol. The results indicate that the heterologous desensitization that follows exposure to bradykinin, ATP or carbachol in NCB-20 cells is mediated by a reduction in a shared pool of intracellular calcium ions.