Effects of radioprotectors on the cAMP and cGMP systems.
The sulphur-containing radioprotectors mercaptoethylamine (MEA), aminoethylisothiourea (AET), 2- aminothiazoline , 4-oxo-2- aminothiazoline , and S-S-3- oxapentane -1,5- diisothiourea , and the radioprotective biogenic amines serotonin, histamine, and dopamine, caused the elevation of cAMP content and intensified the rate of cAMP-dependent protein phosphorylation in tissues of animals following intraperitoneal injection at radioprotective doses. Biogenic amines stimulated the adenylate cyclase activity in membrane preparations from liver, spleen, and small-intestine mucosa; sulphur-containing radioprotectors caused no such effects. None of the radioprotectors affected cAMP and cGMP phosphodiesterases in vitro. AET and MEA inhibited guanylate cyclase in vitro, whereas serotonin and dopamine stimulated the enzyme. A biphasic change in the level of cGMP was observed in tissues after the administration of MEA and AET (more than 2-fold fall by 1-3 min after the administration of drug and 1.4-fold rise after 15-20 min); serotonin and dopamine caused a slow rise in the cGMP level; the cAMP/cGMP ratio in liver showed biphasic changes in level during the 20 min following injection of serotonin. The data obtained support the conclusion that the action of radioprotectors on cellular metabolism in animals may be mediated by the cAMP system. The reciprocal regulation of radioresistance by cAMP and cGMP is unlikely to exist.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D008624:Mercaptoethylamines / Q000494:pharmacology; D051379:Mice; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D001679:Biogenic Amines; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; D013844:Thiazoles; D000338:beta-Aminoethyl Isothiourea; C031363:2-aminothiazoline; D000242:Cyclic AMP; D011494:Protein Kinases; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D013890:Thiourea; D006152:Cyclic GMP