Paradoxical inhibition by aspirin of naloxone-induced adrenocorticotropin secretion in myotonic dystrophy.
The ACTH response to endogenous or exogenous CRH is increased in patients with myotonic dystrophy (DM), possibly because of abnormal function of cAMP-dependent protein kinases in this condition. Arachidonic acid (AA) metabolites are believed to interact with the cAMP-dependent second messenger system activated by CRH; therefore, drugs that interfere with AA metabolism may alter ACTH secretion in DM. In this study, seven DM patients were given naloxone, which stimulates endogenous CRH release, and aspirin, which inhibits the synthesis of prostaglandins from AA via the cyclooxygenase metabolic pathway. Pretreatment with aspirin reduced the mean integrated ACTH response to naloxone by 33% (P < 0.05). However, the corresponding 18% reduction in cortisol levels was not statistically significant (P > 0.10). These findings are in contrast to those of a previous study using an identical protocol, in which aspirin increased the ACTH response to naloxone in six normal volunteers. This difference between DM and control subjects is consistent with the hypothesis that the interaction between AA metabolites and the cAMP-dependent protein kinase-A second messenger system is abnormal in the corticotrophs of persons with DM.
Hockings
G I
GI
University of Queensland Department of Medicine, Greenslopes Hospital, Brisbane, Australia.
Jackson
R V
RV
Grice
J E
JE
Crosbie
G V
GV
Walters
M M
MM
Torpy
D J
DJ
Jackson
A J
AJ
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000097:blood* / Q000503:physiopathology; D009270:Naloxone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011863:Radioimmunoassay; D012680:Sensitivity and Specificity; D013997:Time Factors
D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D001241:Aspirin; D006854:Hydrocortisone