Hormonal activation of adenylate cyclase in macrophage membranes is regulated by guanine nucleotides.

摘要: Many macrophage functions such as chemotaxis, phagocytosis, enzyme secretion, and cytotoxicity are influenced by intracellular cyclic nucleotide levels, but the regulatory mechanisms involved poorly defined. We have developed methods that allowed us to study activation of AC in isolated guinea pig (g.p.) membranes. these membrane preparations could be stimulated approximately twofold guanine nucleotides. not obtain any hormonal membrane-bound absence In presence GTP, however, hormones isoproterenol PGE1 elicited an additional threefold rise activity, which subsided after 15 min. As little 10(-8) M concentrations two induced significant elevations activity. Replacement GTP its nonhydrolyzable analogue Gpp(NH)p resulted a persistent hormone-independent AC, addition enhanced this level activation. Thus, GTP-ase activity is present serves regulate Hormonal stimulation was receptor mediated, because effect beta-adrenergic agonist isoproterenol, PGE1, inhibited blocker propranolol. addition, potency series PG corresponded observed for cAMP production intact g.p. macrophages, i.e., = PGE2 greater than PGA1 PGF2 alpha. preparation alpha-adrenergic agonist, thus demonstrating one means down regulating macrophages. Our studies also showed certain (e.g., agonists, PG) can exert their on whereas other agents lectins or arachidonic acid require components elevate levels The mechanism membranes appears fit model ternary complex, include hormone receptor, protein, transmits signal from AC.