RT Journal Article
SR Electronic
T1 Calcium-induced release from platelet membranes of fatty acids that modulate soluble guanylate cyclase.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 180
OP 186
VO 226
IS 1
A1 R Gerzer
A1 P Hamet
A1 A H Ross
A1 J A Lawson
A1 J G Hardman
YR 1983
UL http://jpet.aspetjournals.org/content/226/1/180.abstract
AB Incubation of rat or rabbit platelet membranes with Ca++ induced the release of modulators of soluble guanylate cyclase. These modulators increased basal activity and inhibited sodium nitroprusside-stimulated activity in the absence or presence of dithiothreitol. The release, but not the effects, of the modulators was inhibited by trifluoperazine and by mepacrine. Indomethacin and oxyphenbutazone did not influence the release or effects of the modulators. The factors were identified as arachidonic and linoleic acids. These fatty acids produced comparable effects on crude soluble guanylate cyclase from platelets and on the homogeneously purified enzyme from bovine lung. In the presence of MgCl2, the maximal increase in basal activity was observed at 10 to 30 microM arachidonic or linoleic acid with the crude enzyme and at 3 to 6 microM with the purified enzyme. Inhibition of basal activity was observed at higher concentrations. Half-maximal inhibition of Mg++-supported, sodium nitroprusside-augmented activity was observed at 3 to 10 microM fatty acid. The effects of arachidonic acid occurred without a lag period and were quickly reversible. These data demonstrate that unsaturated fatty acids can be released from platelet membranes by a Ca++-dependent process in amounts that are high enough to alter soluble guanylate cyclase activity. The data also indicate that unsaturated fatty acids exert their effects on soluble guanylate cyclase without having to be converted to peroxides by other enzymes.