Effect of isatin on nitric oxide-stimulated soluble guanylate cyclase from human platelets.
Isatin, an endogenous indole, has previously been shown to inhibit atrial natriuretic peptide (ANP)-stimulated particulate guanylate cyclase activity. Here, it was shown that it can be transported to human platelets where it inhibited nitric oxide (NO)-stimulated soluble guanylate cyclase activity obtained from human platelets. The effect was most pronounced at 10(-8)M isatin and is the most potent effect of isatin yet observed. The dose response curve was bell shaped with higher doses becoming less effective. The maximal inhibition observed was of 40%. Isatin had no effect on protoporphyrin IX-stimulated guanylate cyclase. Isatin-dependent regulation of ligand-stimulated guanylate cyclases is suggested to promote a stress-induced switch in metabolism.
Medvedev
Alexei
A
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, 10 Pogodinskaya Street, 119932, Moscow, Russia. medvedev@ibmh.msk.su
Bussygyna
Olga
O
Pyatakova
Natalia
N
Glover
Vivette
V
Severina
Irene
I
D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007510:Isatin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D007510:Isatin; D006162:Guanylate Cyclase; D006152:Cyclic GMP