Evidence of specific benzodiazepine binding to myometrial membrane preparations from human pregnant uterus.
The muscle relaxant effect of benzodiazepines (BDZ) is widely held to be mediated at central as well as at peripheral level. In this study we report that crude membrane preparations from the myometrium of pregnant women possess binding sites for [3H]-RO 5-4864, specific ligand for the peripheral type of BDZ receptor. Scatchard analysis shows a high affinity binding site (KD = 3.1 +/- 1.2 nM) and a class of low affinity binding sites (KD greater than 30 nM). Displacement experiments show that various BDZ are differently effective in inhibiting [3H]-RO 5-4864 binding: RO 5-4864 greater than diazepam greater than flunitrazepam greater than lorazepam greater than chlordiazepoxide. In conclusion, these data seem to demonstrate that human myometrium possesses specific binding sites of 'peripheral type' for BDZ. It may be suggested that these binding sites are involved in mediating the myometrial relaxant effect exerted by BDZ. Thus, peripherally active BDZ could be used as tocolytic agents, avoiding BDZ central effects.
D000328:Adult; D001569:Benzodiazepines / Q000378:metabolism*; D001570:Benzodiazepinones / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002707:Chlordiazepoxide / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D006801:Humans; D008140:Lorazepam / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism*
D001570:Benzodiazepinones; D011956:Receptors, Cell Surface; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D005445:Flunitrazepam; D002707:Chlordiazepoxide; D008140:Lorazepam; D003975:Diazepam