Detail of "37762-06-4"

Reference

Effects of antiallergic agents, compound 48/80, and some reference inhibitors on the activity of partially purified human lung tissue adenosine cyclic 3',5'-monophosphate and guanosine cyclic 3',5'-monophosphate phosphodiesterases

Effects of antiallergic agents, compound 48/80, and some reference inhibitors on the activity of partially purified human lung tissue adenosine cyclic 3',5'-monophosphate and guanosine cyclic 3',5'-monophosphate phosphodiesterases. Bergstrand, Hakan; Kristoffersson, Jan; Lundquist, Britta; Schurmann, Annika (Res. Dev. Lab., AB Draco, Lund, Swed.). Mol. Pharmacol., 13(1), 38-43 (English) 1977.Some commonly used reagents like 104-29-0 and 58-55-9 are used in this experiment. CODEN: MOPMA3. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Various compds., some of which influence immediate allergic reactions in different ways, were examd. for inhibitory effects on partially purified human lung tissue cyclic nucleotide phosphodiesterases. Some of the compds. reported to possess antiallergic properties were more potent as inhibitors of a low-Km, cyclic GMP phosphodiesterase [9068-52-4] than of a corresponding low-Km, cyclic AMP phosphodiesterase [9036-21-9]. For MB 22,948 (I) [37762-06-4], ICI 74917 (II) [54545-84-5], and disodium cromoglycate (III) [15826-37-6] this selectivity was remarkable; to produce 50% inhibition of enzyme activity, a 10-100-fold lower concn. of these agents was required with the former enzyme than with the latter. Compd. 48/80, on the other hand, showed high selectivity as an inhibitor of the cyclic AMP phosphodiesterase. Among the ref. phosphodiesterase inhibitors examd, theophylline [58-55-9], 3-isobutyl-1-methylxanthine [28822-58-4], and papaverine-HCl [61-25-6] inhibited both low-Km enzymes to a comparable degree, whereas Ro20-1724 (IV) [29925-17-5] was pronouncedly more active toward the cyclic AMP-specific enzyme. Most compds. examd. also inhibited the activty of a high-Km cyclic 3',5'-nucleotide phosphodiesterase [9040-59-9] which hydrolyzes cyclic AMP and cyclic GMP at comparable rates. Pronounced inhibitory potency was recorded for dicumarol [66-76-2], doxantrazole [51762-95-9], compd. 48/80, and papaverine, whereas II was only slightly effective with this enzyme. .

The effects of alkylated xanthines on cyclic AMP accumulation in dog thyroid slices exposed to carbamylcholine

The effects of alkylated xanthines on cyclic AMP accumulation in dog thyroid slices exposed to carbamylcholine. Miot, Francoise; Erneux, Christophe; Wells, Jack N.; Dumont, Jacques E. (Sch. Med., Free Univ. Brussels, Brussels B-1070, Belg.). Mol. Pharmacol., 25(2), 261-6 (English) 1984. CODEN: MOPMA3. ISSN: 0026-895X. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 1 Alkylated xanthines, Ro 20-1724 [29925-17-5] and M & B 22948 [37762-06-4], were studied as inhibitors of partially purified dog thyroid cyclic nucleotide phosphodiesterase [50812-31-2] and for their ability to alter cAMP [60-92-4] and cGMP [7665-99-8] accumulation in dog thyroid slices that had been stimulated with TSH [9002-71-5] and(or) carbamylcholine [462-58-8]. 1-Methyl-3-isobutylxanthine (MIX) [28822-58-4] and 7-benzyl-MIX [58481-23-5] were the most potent inhibitors of phosphodiesterase activities in the crude sol. and particulate fractions but exhibited no selectivity for inhibiting cAMP or cGMP hydrolysis. In dog thyroid slices stimulated by TSH and in the absence of carbamylcholine, Ro 20-1724 and 1-isoamyl-MIX (IIX) [63908-26-9] were the most effective compds. to potentiate the accumulation of cAMP. The rank order of abilities to potentiate cAMP accumulation in dog thyroid slices stimulated by TSH paralleled the rank order of potencies to inhibit the cAMP-specific phosphodiesterase. In the presence of carbamylcholine, the obsd. decrease in cAMP levels was attenuated by MIX, 8-methoxymethyl-MIX (8-MeOMe-MIX) [73586-20-6], 7-benzyl-MIX, and M & B 22948, the most potent inhibitors of the calmodulin-sensitive phosphodiesterase. MIX, 8-MeOMe-MIX, and 7-benzyl-MIX inhibited the cGMP-stimulated phosphodiesterase in the same rank order of potencies as the calmodulin-sensitive enzyme, but M & B 22948 did not significantly inhibit the cGMP-stimulated enzyme activity. IIX and Ro 20-1724 did not alter the carbamylcholine-induced inhibition of cAMP accumulation. Selective inhibitors of the calmodulin-sensitive phosphodiesterase are able to relieve in vitro the carbamylcholine-induced inhibition of cAMP accumulation, whereas selective inhibitors of the cAMP-specific phosphodiesterase are not. This suggests that in the dog thyroid, in the presence of carbamylcholine, the calmodulin-sensitive phosphodiesterase is activated by an increase in free Ca2+ level and becomes the dominant isozyme of cAMP catabolism.