SELECTIVE ENHANCEMENT BY SERUM FACTORS OF CYCLIC-AMP ACCUMULATION IN RAT MICROGLIAL CULTURES

Using purified microglial cultures obtained from the neonatal rat brai n we found that media containing fetal calf serum (as well as human, h orse and goat sera) enhanced by about 3-fold the accumulation of cycli c AMP induced by the beta-adrenergic agonist isoproterenol and did not affect in a significant way that induced by the direct adenylyl cycla se stimulator forskolin. The effect of fetal calf serum was (i) dose d ependent, and statistically significant also at serum concentrations b elow 1%; (ii) rapidly lost (half life of about 15 min) when the serum- containing medium was exposed to microglia, astrocytes or neuroblastom a cells; (iii) present also when cyclic AMP accumulation was enhanced by prostaglandin E(2) or by cholera toxin; (iv) absent on basal cyclic AMP levels. When media containing fetal calf serum or the other mamma lian sera mentioned above were tested on astrocyte cultures, an inhibi tory, rather than enhancing activity encyclic AMP levels was observed, indicating that the facilitatory factor(s) present in serum acts spec ifically on microglial cells. Moreover, in astrocytes the effect of se rum was identical when tested on basal and on isoproterenol or forskol in-stimulated cyclic AMP levels. Thus, the mechanism of cyclic AMP inh ibition in astrocytes is unrelated to the mechanism of activation in m icroglia. Our observations suggest that serum contains factor(s), prom ptly cleared by different cell types. Such factors may interact with s o far unidentified microglial receptors responsible for a Facilitation of G protein-mediated activation of adenylyl cyclase. Regulation of t he cyclic AMP cascade at this step has not been described previously, and may be important for the modulation of microglial functions contro lled by the cyclic nucleotide. Copyright (C) 1996 Elsevier Science Ltd .