Cyclosporine A increases serum cortisol levels in rabbits.
P-glycoprotein (P-gp), a membrane protein that was originally found to be involved in the efflux of cytotoxic drugs out of the tumor cells, is also present in a variety of normal human and animal tissues, such as the adrenal cortex. The function of P-gp in the adrenal cortex has not been defined yet. The aim of our study was to determine whether the blockade of P-gp by cyclosporine A (CsA) dissolved in Cremophor EL (Crem) inhibits cortisol secretion in rabbits. In 14 rabbits, the baseline and ACTH stimulated serum cortisol levels were measured before and after CsA treatment. Seven rabbits were treated with 2 x 30 mg/kg CsA and seven with 2 x 90 mg/kg CsA injected s.c. Serum cortisol levels were determined by radioimmunoassay adjusted for expected values. The whole blood CsA levels were determined by a commercially available fluorescence polarization immunoassay. Serum cortisol levels, both baseline and ACTH stimulated, significantly increased after both low and high dose CsA treatment. The increase was dose dependent. The mean baseline cortisol levels increased from 5.7 (SD = 6.3) to 15.0 nmol/l (SD = 7.2) in the low dose group and from 7.7 (SD = 4.9) to 44.9 nmol/l (SD = 13.8) in the high dose group. The mean cortisol levels 8 h after ACTH stimulation increased from 53.3 (SD = 34.5) to 106.0 nmol/l (SD = 33.0) in the low dose group and from 47.7 (SD = 12.2) to 153.0 nmol/l (SD = 55.1) in the high dose group.(ABSTRACT TRUNCATED AT 250 WORDS)
Cufer
T
T
Institute of Oncology, Ljubljana, Slovenia.
Vrhovec
I
I
Skrk
J
J
Pfeifer
M
M
Pajk
B
B
Zakotnik
B
B
Filipic
B
B
Rode
B
B
Sikic
B I
BI
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D011817:Rabbits; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016572:Cyclosporine; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone