Uptake of CD-349 and nitrendipine into bovine intrapulmonary artery and vein.
The uptake of CD-349 into the bovine intrapulmonary artery (BPA) and vein (BPV) was examined and characteristics of this newly synthesized 1,4-dihydropyridine Ca2+ antagonist were compared with those of nitrendipine. One hundred minutes after initiation of incubation of the vessels, the uptake of [3H]CD-349 and [3H]nitrendipine reached a plateau. The concentrations of CD-349 inside the muscle cell of the BPA and BPV were 11.1 and 6.8 times higher than that of the incubation medium, respectively, and concentrations of nitrendipine in the BPA and BPV were 8.6 and 6.1 times higher, respectively. The degree of uptake was not influenced by the lowering the incubation temperature nor by adding 2,4-dinitrophenol. The partition coefficient of CD-349 measured in the corn oil/Ringer and octanol/Ringer systems was greater than the partition coefficient of nitrendipine, independent of the concentration tested. These results suggest that CD-349 permeates smooth muscle membrane by passive diffusion and accumulates inside the muscle cells, much in the same manner as seen with nitrendipine. The lipid solubility of DC-349 presumably accounts for these events.
Tanaka
M
M
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Muramatsu
M
M
Aihara
H
H
D019297:2,4-Dinitrophenol; D000818:Animals; D002417:Cattle; D004095:Dihydropyridines / Q000378:metabolism*; D004140:Dinitrophenols / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism*; D011667:Pulmonary Veins / Q000378:metabolism*; D013696:Temperature; D014475:Uncoupling Agents / Q000494:pharmacology
D004095:Dihydropyridines; D004140:Dinitrophenols; D014475:Uncoupling Agents; C054179:CD 349; D009568:Nitrendipine; D019297:2,4-Dinitrophenol