Spironolactone causes a rapid down regulation of sigma recognition sites in guinea pig brain and liver.
The effect of dosing guinea pigs with spironolactone (100 mg/kg twice daily for 3 days) upon the sigma recognition site labelled with [3H]-DTG was investigated. Animals were dosed with 100 mg/kg spironolactone twice a day for 3 days. Spironolactone treatment caused a decrease in sigma radioligand binding in membranes prepared from liver and brain but not in adrenals or testes. Saturation analysis of [3H]-DTG radioligand binding in the brain indicated that the decrease in specifically bound [3H]-DTG binding was due to a reduction in receptor number with no change in affinity. This method for the selective depletion of brain and liver sigma recognition sites will provide a useful tool for exploring the functional significance of this site.
Knight
A R
AR
Merck Sharp and Dohme, Neuroscience Research Centre, Harlow, Essex.
Wyatt
C
C
Middlemiss
D N
DN
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D006146:Guanidines / Q000378:metabolism; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017480:Receptors, sigma; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects / Q000378:metabolism
D006146:Guanidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; D013148:Spironolactone; C050232:1,3-ditolylguanidine