Relationship between Fc.gamma.2b receptor and adenylate cyclase of a murine macrophagelike cell line, P388D1

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Abstract
The relationship between Fc receptor specific for IgG2b (Fc.gamma.2bR) and membrane adenylate cyclase was investigated. The specific binding of IgG2b immune complexes to P388D1 cell surface Fc.gamma.2bR was found to inhibit the basal, forskolin-stimulated, and NaF-stimulated activities of membrane adenylate cyclase by 53%, 57%, and 31%, respectively. On the other hand, of IgG2a immune complexes to cell surface Fc.gamma.2aR increased the basal activity about 2.5-fold and the forskolin- and NaF-stimulated activities slightly. The fusion of liposomes containing Fc.gamma.2bR, which was obtained as phosphatidylcholine (PC) binding protein as previously described, with the cyc- membrane preparations reuslted in the marked suppression of membrane adenylate cyclase, whereas the fusion of liposomes containing Fc.gamma.2a, which was obtained as IgG-binding protein, led to about a 2.7-fold increase. The Fc.gamma.2bR-mediated inhibition of adenylate cyclase may be due to the temporary change of the lipid environment caused by the action of phospholipase A2, which was previously shown to be associated with Fc.gamma.2bR, since (1) addition of snake venom phospholipase A2 or cholate-solubilized PC-binding protein to P388D1 membrane was found to inhibit adenylate cyclase in a dose-dependent manner, (2) prior treatment of snake venom phospholipase A2 or PC-binding protein with a specific inhibitor, p-bromophenacyl bromide significantly reduced their inhibitory action, and (3) a product of phospholipase A2 action, arachidonic acid, was found to be an effective inhibitor of membrane adenylate cyclase, whereas the other product, lysophosphatidylcholine, was much less inhibitory than arachidonic acid. Arachidonic acid appeared to interfere with the functions of both guanine nucleotide-binding stimulatory (Gs) protein and the catalytic subunit of adenylate cyclase, since exogenously added arachidonic acid significantly suppressed the GTPase activity of P388D1 membrane and the forskolin response of the adenylate cyclase activity of Gs protein deficient cyc- membrane. The primary site of action of lysophosphatidylcholine is not clear but may be other than Gs protein and/or the catalytic subunit, since it did not change either GTPase activity of P388D11 membrane or the response to forskolin of adenylate cyclase of cyc- membrane. The Fc.gamma.2b/phospholipase A2 mediated inhibition of adenylate cyclase would be a transient event in viable cells, since phospholipase A2 did not inhibit adenylate cyclase in the presence of microsomal fraction, mitochondria, and coenzyme A, suggesting the occurrence of rapid acylation of CoA and reacylation of lysolecithin.

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