CARBACHOL INCREASES INTRACELLULAR FREE CALCIUM IN CULTURED RAT MICROGLIA

Microglia are resident macrophages in the CNS and have been shown to e xhibit immune system responses common to other macrophages, including phagocytosis, secretion of superoxide anions, and secretion of regulat ory and trophic factors such as interleukin-1. Phagocytosis and oxidat ive burst by macrophages are often reported to be preceded by an incre ase in cytosolic free calcium. In addition, a variety of compounds, in cluding neuroactive peptides, have been shown to elicit such calcium r esponses in various macrophage preparations. The results presented dem onstrate that cultured rat microglia respond to exposure to carbachol with an increase in intracellular free calcium which is atropine-sensi tive and the result of the release of calcium from intracellular store s. Norepinephrine also induced increases in free calcium, whereas the metabotropic glutamate agonist 1S,3R-ACPD, serotonin, adenosine and AT P did not. These results suggest that microglia can respond to select neurotransmitters, and that there may exist a signaling loop between n eurons and microglia. Furthermore, since cholinergic fibers have been shown to infiltrate neuritic plaques in Alzheimer's disease (AD) and m icroglia have been reported to be activated in plaques, these results suggest that interactions between select neurotransmitters and microgl ia may play a key role in neurodegenerative diseases.