TY - JOUR
T1 - Effects of prochlorperazine on the function of integral membrane proteins
AU - Dannenberg, Andrew
AU - Zakim, David
N1 - Funding Information:
Acknowledgements--This work was supported in part by the National Science Foundation (DMB 8504014).
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1988/4/1
Y1 - 1988/4/1
N2 - We have studied the effects of prochlorperazine on the activities of UDP-glucuronosyltransferase and glucose-6-phosphatase (glucose-6-P'ase) in rat liver microsomes. The activity of UDP-glucuronosyltransferase was increased in a graded fashion by addition of prochlorperazine. Maximal stimulation occurred at 1 mg prochlorperazine to 2 mg microsomal protein, which resulted in a 6-fold increase in activity. However, with smaller concentrations of drug, there was a time-dependent increase in the activity of UDP-glucuronosyltransferase. Sensitivity of UDP-glucuronosyltransferase to activation by UDP-N-acetylglucosamine was lost after treatment of microsomes with prochlorperazine. These results indicate that prochlorperazine causes a profound reorganization of the interactions between lipids and enzyme since the activity and allosteric properties of UDP-glucuronosyltransferase are known to depend on interactions with lipids in a gel phase. Glucose-6-P'ase also was activated in a graded fashion by prochlorperazine; 1 mg of drug/2 mg microsomal protein resulted in a 60% increase in activity. The temperatyre-dependent instability of glucose-6-P'ase was increased by treatment of microsomes with prochlorperazine and could be prevented only partially by substrate. We conclude that prochlorperazine disrupts the structural organization between lipids and proteins in microsomal membranes, altering thereby the activity and regulation of at least two different integral membrane proteins.
AB - We have studied the effects of prochlorperazine on the activities of UDP-glucuronosyltransferase and glucose-6-phosphatase (glucose-6-P'ase) in rat liver microsomes. The activity of UDP-glucuronosyltransferase was increased in a graded fashion by addition of prochlorperazine. Maximal stimulation occurred at 1 mg prochlorperazine to 2 mg microsomal protein, which resulted in a 6-fold increase in activity. However, with smaller concentrations of drug, there was a time-dependent increase in the activity of UDP-glucuronosyltransferase. Sensitivity of UDP-glucuronosyltransferase to activation by UDP-N-acetylglucosamine was lost after treatment of microsomes with prochlorperazine. These results indicate that prochlorperazine causes a profound reorganization of the interactions between lipids and enzyme since the activity and allosteric properties of UDP-glucuronosyltransferase are known to depend on interactions with lipids in a gel phase. Glucose-6-P'ase also was activated in a graded fashion by prochlorperazine; 1 mg of drug/2 mg microsomal protein resulted in a 60% increase in activity. The temperatyre-dependent instability of glucose-6-P'ase was increased by treatment of microsomes with prochlorperazine and could be prevented only partially by substrate. We conclude that prochlorperazine disrupts the structural organization between lipids and proteins in microsomal membranes, altering thereby the activity and regulation of at least two different integral membrane proteins.
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U2 - 10.1016/0006-2952(88)90779-4
DO - 10.1016/0006-2952(88)90779-4
M3 - Article
C2 - 2833274
AN - SCOPUS:0023864375
VL - 37
SP - 1259
EP - 1262
JO - Biochemical pharmacology
JF - Biochemical pharmacology
SN - 0006-2952
IS - 7
ER -