SPHINGOMYELIN METABOLITES A S SECOND MESSENGERS IN AIRWAY SMOOTH MUSCL E CELL P ROLIFERATION

Sphingolipid metabolism was examined in guinea-pig airway smooth muscle cells stimulated by platelet-derived growth factor (PDGF) and 4β-phorbol 12- myristate 13-acetate (PMA), as mitogens and bradykinin (BK) as non-mitogen. Stimulation of the cells by PMA and PDGF for 60 min. at 37°C induced the following changes in sphingolipid metabolites: in cells prelabeled with PH] palmitate, a 1.2 fold increase in radio-labeled sphingosine, a concomitant 20% decrease in radio-labeled ceramide and no significant change in sphingomyelin level. Stimulation of the cells by BK induced no changes in sphingolipid levels at any time tested. This study demonstrates the existence of a "sphingomyelin cycle" in airway smooth muscle cells. Such sphingolipid cycles may function in a signal transduction pathway and in cellular proliferation.