Partition of Ca2+ antagonists in brain plasma membranes.
The partition coefficients (Kp) of three prototype Ca2+ antagonists, nitrendipine, (-)-desmethoxyverapamil and flunarizine were determined in native synaptic plasma membranes (SPM) isolated from sheep brain cortex and in liposomes prepared with the total lipids extracted from the membranes. We found that at 25 degrees and at 5 x 10(-6) M drug concentration the Kp values of the drugs for native SPM are higher than those obtained for liposomes, and are of the order of 334 +/- 53, 257 +/- 36 and 23 X 10(3) for nitrendipine, (-)desmethoxyverapamil and flunarizine, respectively, whereas the Kp values in liposomes are 190 +/- 41, 118 +/- 10 and 6 x 10(3) for the same drugs. The results suggest that the presence of membrane proteins favors the incorporation of the drugs in the membranes. Furthermore, the Kp values of the three Ca2+ antagonists studied increase with temperature in native membranes, but not in liposomes. It is concluded that the physical partitioning in membranes of drugs which act on Ca2+ channels may play some role in the mechanism of interaction of these drugs with the Ca2+ channel proteins.
Carvalho
C M
CM
Department of Zoology, University of Coimbra, Portugal.
Oliveira
C R
CR
Lima
M P
MP
Leysen
J E
JE
Carvalho
A P
AP
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D005444:Flunarizine / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes; D009568:Nitrendipine / Q000378:metabolism*; D012756:Sheep; D013570:Synaptic Membranes / Q000378:metabolism*; D014700:Verapamil / Q000031:analogs & derivatives* / Q000378:metabolism
D002121:Calcium Channel Blockers; D008081:Liposomes; C043184:4-desmethoxyverapamil; D009568:Nitrendipine; D014700:Verapamil; D005444:Flunarizine