Effect of psychoactive drugs on lymphocyte neuropeptides.
The concentrations of beta-endorphin and cholecystokinin were measured in lymphocytes obtained from young or old rats and from humans at different ages. Both in rats and humans, beta-endorphin and cholecystokinin increase with age; also in vitro, after 48-h culturing, the concentrations of beta-endorphin and cholecystokinin in lymphocytes obtained from humans of different ages changed with the same pattern observed in ex vivo experiments. In the human, beta-endorphin in lymphocytes shows a circadian rhythm that shifts approximately 6 h when compared to plasma ACTH and cortisol rhythm. The HPLC analysis of the molecular forms of beta-endorphin in lymphocytes revealed the presence of N-acetyl-beta-endorphin, with a ratio of beta-endorphin to N-acetyl-beta-endorphin ranging from 1 to 2. The concentrations of beta-endorphin and cholecystokinin were also measured in lymphocytes obtained from rats and human subjects undergoing different pharmacological treatments. In rat, the serotonin receptor antagonist metergoline decreased basal concentrations of the opioid peptide and blocked the increase of beta-endorphin concentrations induced by the serotonin precursor 5-hydroxytryptophan and the tricyclic antidepressant chlorimipramine. Also in the human, the antidepressant drug chlorimipramine increased lymphocyte beta-endorphin concentrations. In contrast to what was observed for beta-endorphin, cholecystokinin concentrations were not affected by the modulation of the serotoninergic system. Chronic treatment of rats with the dopamine receptor antagonist haloperidol induced an increase of beta-endorphin concentrations in lymphocytes that was reversed by the concomitant treatment with the dopamine receptor agonist bromocriptine, which when given alone decreased the basal concentrations of the peptide. In the human, haloperidol increased concentrations of beta-endorphin after both 24 h and chronic treatment, while cholecystokinin was never affected. Finally, beta-endorphin, but not cholecystokinin, increases both in rat and human lymphocytes after treatment with the GABA agonist sodium valproate.
Sacerdote
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Department of Pharmacology, School of Medicine, University of Milan, Italy.
Ciciliato
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Rubboli
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Panerai
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D000818:Animals; D002766:Cholecystokinin / Q000032:analysis*; D004298:Dopamine / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000032:analysis / Q000187:drug effects*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000502:physiology; D001615:beta-Endorphin / Q000032:analysis*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D011619:Psychotropic Drugs; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D001615:beta-Endorphin; D002766:Cholecystokinin; D004298:Dopamine