Agonist-stimulated Ca2+ response in neutrophils from patients with primary alcoholism and alcoholized healthy subjects.
The sensitivity of the inositol phosphate (IP)/Ca2+-second messenger generating system was assessed in neutrophils from healthy volunteers before and after ingestion of approximately 1%o ethanol for 2 h. In addition, isolated neutrophils from healthy subjects were incubated with ethanol in vitro. Furthermore, the sensitivity of the IP/Ca2+ system was evaluated in neutrophils from alcoholic patients in the state of active drinking, and after 2-3 weeks and 6 months of abstinence. EC50 values of the concentration-response curves obtained by agonist stimulation with formyl-methionyl-leucylphenylalanine (fMLP) of the intracellular Ca2+ accumulation were determined as an indicator of the sensitivity of the system. Ingestion of ethanol by healthy volunteers (both in the ex vivo and in vitro experiments) induced a rightward shift of the concentration-response curve (higher EC50 values) in neutrophils, indicating a reduced sensitivity to agonist stimulation evoked by ethanol. The sensitivity of the Ca2+ response in neutrophils from alcoholic patients decreased intraindividually after a period of 2-3 weeks of abstinence (higher EC50 values) and was at this time also significantly lower compared to a group of matched healthy controls In contrast, the maximal Ca2+ release induced by a saturating concentration of fMLP was increased after 2-3 weeks of abstinence, both intraindividually and in comparison to healthy controls. These alterations of the EC50 values and the maximal Ca2+ response were normalized after 6 months of abstinence. It is concluded that ethanol attenuates the sensitivity of the IP/Ca2+ system in neutrophils in healthy subjects. In neutrophils from alcoholic subjects complex alterations appear to persist up to several weeks, which are only normalized after a prolonged period of abstinence.
Gann
H
H
Department of Psychiatry and Psychotherapy, University of Freiburg, Germany.
Ebersholdt
M
M
Adamovic
K
K
van Calker
D
D
D000328:Adult; D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D007295:Inositol Phosphates; D000431:Ethanol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium