Stimulation of cAMP formation by prostaglandin D 2 in primary cultures of bovine adrenal medullary cells: identification of the responsive population as fibroblasts

Abstract

In primary cultures of bovine adrenal medulla, chromaffin cells responded to prostaglandin (PG) E 2 by stimulating phosphoinositide metabolism (Yokohama et al. (1988) J. Biol. Chem. 263, 1119–1122). In contrast, nonchromaffin cells were found to respond to PGD 2 by elevating their intracellular cAMP level. The formation of cAMP was detected at as low as 0.1 nM PGD 2 and increased more than 100-fold over the basal level at 0.1 μM, and the response was specific for PGD 2 (> PGE i > PGE 2 > PGF 2 α = PGI 2). The magnitude of cAMP formation and its specifity to PGD 2 were retained throughout a 40-day culture period. Based on the inhibitory effect of cis-4-hydroxy- l -proline, an inhibitor of collagen synthesis, on cAMP formation, morphology, and immunoreactivity of cells to anti-collagen type I antiserum, the responsive cells were identified as fibroblasts. These results taken together demonstrate that the adrenal medulla is composed of chromaffin and nonchromaffin cells, which respond to PGE 2 and PGD 2, respectively, by two different signal transduction pathways. The cAMP formation by PGD 2 was also observed in fibroblasts from bovine embryonic trachea among cell lines tested, suggesting that some populations of fibroblasts responsive to PGD 2 exist in various tissues and may discriminate the signal from that of PGE 1 or PGE 2.