title: Selective activation of particulate guanylate cyclase by a specific class of porphyrins.
abstract: Guanylate cyclase was activated 3- to 10-fold by hemin in a dose-dependent manner in membranes prepared from homogenates of rat lung, C6 rat glioma cells, or B103 rat neuroblastoma cells. Maximum activation was observed with 50 to 100 microM hemin with higher concentrations being inhibitory. Activation was observed when Mg2+-GTP but not when Mn2+-GTP was used as the substrate. Increased enzyme activity reflected selective activation of the particulate form of guanylate cyclase; hemin inhibited the soluble form of guanylate cyclase 70 to 90% over a wide range of concentrations. Activation was not secondary to proteolysis since a variety of protease inhibitors failed to alter stimulation by hemin. Protophorphyrin IX had little effect on particulate guanylate cyclase activity and sodium borohydride almost completely abolished hemin-dependent activation. These data suggest a requirement for the ferric form of the porphyrin-metal chelate for activation. However, agents which interact with the iron nucleus of porphyrins, such as cyanide, had little effect on the ability of hemin to activate guanylate cyclase. The stimulatory effects of hemin were observed in the presence of detergents such as Lubrol-PX, and highly purified particulate enzyme could be activated to the same extent as enzyme in native membranes. These data suggest that the interaction of porphyrins with particulate guanylate cyclase is complex in nature and different from that with the soluble enzyme.
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D005910:Glioma / Q000201:enzymology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008566:Membranes / Q000201:enzymology; D009447:Neuroblastoma / Q000201:enzymology*; D011166:Porphyrins / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D011166:Porphyrins; D006427:Hemin; D006162:Guanylate Cyclase