Impairment of adrenergic-induced proopiomelanocortin-related peptide release in heroin addicts.
The effects of iv stimulation with clonidine on plasma levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), cortisol, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) were tested in a group of 10 healthy volunteers and in 8 heroin abusers. Hormones were measured either by direct radioimmunoassay (RIA) (GH, cortisol) or after plasma extraction and Sephadex G-75 column chromatography (beta-LPH and beta-EP) or by immunoradiometric assay (IRMA) (ACTH). Plasma levels of GH increased in a similar fashion in the two groups. In the controls, clonidine induced release of beta-LPH and beta-EP after 30 min (from 8.9 +/- 1.0 to 19.1 +/- 4.6 fmol/ml, P less than 0.01 and from 8.1 +/- 0.6 to 17.9 +/- 4.6, P less than 0.01) and of ACTH after 60 min (from 12.1 +/- 1.8 to 18.1 +/- 1.8, P less than 0.05) while in addicts beta-EP but not beta-LPH showed a significant increase (from 8.5 +/- 0.7 to 19.8 +/- 4.2, P less than 0.05), 90 min after the injection. In heroin addicts, plasma cortisol levels decreased continuously after clonidine stimulation while in controls they showed a biphasic pattern, decreasing until the 60th min (from 135.2 +/- 30.4 ng/ml to 74.0 +/- 13.3, P less than 0.05) and regaining basal levels 1 h later (122.0 +/- 24.8, P less than 0.05 vs 60th min value). These data demonstrate the existence in human beings of noradrenergic control of proopiomelanocortin (POMC)-related peptides and indicate that chronic opiate abuse greatly interferes with this control. Clonidine-induced release of plasma beta-EP may be of importance with regard to its therapeutic effects in detoxification.
Facchinetti
F
F
Volpe
A
A
Nappi
G
G
Petraglia
F
F
Genazzani
A R
AR
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003000:Clonidine / Q000494:pharmacology*; D004723:Endorphins / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006556:Heroin Dependence / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D001615:beta-Endorphin; D008083:beta-Lipotropin / Q000097:blood
D000316:Adrenergic alpha-Agonists; D004723:Endorphins; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D008083:beta-Lipotropin; D003000:Clonidine; D006854:Hydrocortisone