Inhibitory effect of NZ-105, a 1,4-dihydropyridine derivative, on cyclic nucleotide phosphodiesterase activity.
The effects of NZ-105, a 1,4-dihydropyridine calcium antagonist, on the intracellular cyclic nucleotide system were investigated in-vitro. In rabbit isolated aorta, both NZ-105 (1 and 10 microM) and nicardipine significantly and in a concentration-dependent manner increased intracellular cyclic AMP and cyclic GMP content. NZ-105 inhibited bovine cardiac phosphodiesterase activity (Ki 30 microM) by competitive antagonism. The concentration ranges for inhibition were consistent with the range of increases in cyclic nucleotides.
Yamashita
T
T
Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd., Saitama, Japan.
Masuda
Y
Y
Sakai
T
T
Tanaka
S
S
Kasuya
Y
Y
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors*; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009529:Nicardipine / Q000494:pharmacology; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011817:Rabbits
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D009529:Nicardipine; D000242:Cyclic AMP; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine