ROLE OF THE SIGMA RECEPTOR IN THE INHIBITION OF [H-3] NORADRENALINE UPTAKE IN BRAIN SYNAPTOSOMES AND ADRENAL CHROMAFFIN CELLS

被引:30
作者
ROGERS, C [1 ]
LEMAIRE, S [1 ]
机构
[1] UNIV OTTAWA,FAC MED,DEPT PHARMACOL,451 SMYTH RD,OTTAWA K1H 8M5,ONTARIO,CANADA
关键词
PHENCYCLIDINE RECEPTOR; SIGMA RECEPTOR; CATECHOLAMINE REUPTAKE; SYNAPTOSOMES; CHROMAFFIN CELLS; ADRENAL MEDULLA;
D O I
10.1111/j.1476-5381.1991.tb12352.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Rat brain synaptosomes and cultured bovine adrenal chromaffin cells were used to monitor the inhibitory effects of phencyclidine (PCP) and sigma (sigma)-receptor ligands on the uptake of [H-3]-noradrenaline ([H-3]-NA). 2 A Na+-dependent high affinity uptake was observed in synaptosomes (30-degrees-C) and chromaffin cells (37-degrees-C) with K(m) of 0.22 and 0.56-mu-M and V(max) of 2.5 pmol min-1 mg-1 protein and 0.7 pmol min-1 per 10(6) cells, respectively. 3 PCP and haloperidol inhibited the high affinity uptake with IC50 of 0.17 and 0.42-mu-M, respectively in synaptosomes and 0.24 and 0.47-mu-M, respectively in adrenal chromaffin cells. 4 A close correlation (r = 0.96) was established between the ability of various PCP and sigma-receptor ligands to inhibit [H-3]-NA uptake in both systems: PCP > TCP > haloperidol > 3-(+)-PPP > MK-801 greater-than-or-equal-to (-)-butaclamol > (+)-SKF-10047 > DTG. Spiperone and opioid receptor ligands were inffective at 20-mu-M. 5 These results indicate that the central and peripheral inhibitory effects of PCP and sigma-receptor ligands on [H-3]-NA uptake involves a receptor (sigma-1-like) which is distinct from that (PCP2) recognized for the inhibition of [H-3]-dopamine uptake by PCP.
引用
收藏
页码:1917 / 1922
页数:6
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