Inhibition of mammalian soluble guanylate cyclase activity by adenosine 5'-tetraphosphate, guanosine 5'-tetraphosphate and other nucleotides.
The effects of a variety of purine and pyrimidine nucleotides were tested for their capacity to inhibit mammalian soluble guanylate cyclase activity. Adenosine 5'-tetraphosphate (ATetP), ATP, ADP, AMP, guanosine 5'-tetraphosphate (GTetP) and GDP were found to inhibit soluble guanylate cyclase activity from rat lung and other mammalian tissues. The corresponding cytosine and thymine nucleotides showed little or no inhibitory activity, except for thymidine 5'-tetraphosphate, which inhibited glanylate cyclase activity but to a lesser extent than did the purine nucleoside tetraphosphates. ATetP and GTetP were found to be potent inhibitors of soluble guanylate cyclase activity from rat, guinea pig and mouse lung, rat heart and rat brain. Both purine nucleoside tetraphosphates were competitive inhibitors of the rat lung soluble enzyme. ATetP and GTetP had Ki values of 1 muM and 2.5 muM, respectively. The experimental data suggest that purine nucleoside tetraphosphates, and perhaps other purine nucleotides, may play a biologic role in modulating mammalian soluble guanylate cyclase activity.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D012995:Solubility
D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D008345:Manganese; D006162:Guanylate Cyclase