Synaptic vesicles have a Ca2+-dependent protein kinase system that may play a role in mediating Ca2+-stimulated neurotransmitter release and vesicle function. Calcium's ability to initiate norepinephrine release and protein phosphorylation in synaptic vesicle preparations was shown to be stimulated by the presence of an endogenous heat-stable vesicle protein fraction. The heat stability and characteristics of this endogenous vesicle fraction were similar to those of calmodulin (Ca2+-dependent regular protein) isolated from rat and bovine brain. Calmodulin, like endogenous heat-stable vesicle factor, restored calcium's ability to stimulate vesicle neurotransmitter release and protein kinase activity. Calmodulin-like vesicle protein and purified calmodulin were also equally effective in stimulating cyclic nucleotide-dependent phosphodiesterase, further indicating that these two proteins are functionally equivalent. Depolarization-dependent Ca2+ uptake in intact synaptosomes simultaneously stimulated release of neurotransmitter and phosphorylation of particular synaptic vesicle proteins that were shown in the isolated vesicle preparation to be dependent on Ca2+ and calmodulin. The results suggest that calcium's effects on neurotransmitter release and presynaptic nerve terminal protein phosphorylation may be mediated by endogenous calmodulin-like proteins.

LPS activation of murine macrophage metabolism and arginase production may be mediated by products of B lymphocytes. Splenic nonadherent cells, containing both B and T lymphocytes, splenic T cells, and thymocytes all stimulated macrophage glucose metabolism in co-culture. Supernatants derived from preculturing each of these cells in the absence of serum or other exogenous stimulant were also active in enhancing macrophage glucose utilization. When lipopolysaccharides were used to stimulate the lymphocyte populations, only the B lymphocyte containing NASC and purified B cells exhibited increased stimulatory activity. Thus, it appears that LPS does not directly activate T cells to produce macrophage-activating factors. The converse does not appear to be true, however, because LPS-stimulated macrophages enabled thymocytes to exhibit an enhanced ability to stimulate further macrophage glucose utilization. The active supernatant from NASC was heat resistant and remains to be chemically defined. These experiments clearly demonstrate that LPS-induced macrophage activation may be mediated by the products of lymphocytes, and that products derived from nonactivated lymphocytes are capable of stimulating macrophage metabolism and arginase production.