Effect of brain mast cells degranulation on the corticosterone response to stimulation of central opioid receptors in rats.
The influence of brain mast cells degranulation, exerted by compound 48/80 given intracerebroventricularly, on the opioid-induced stimulation of the pituitary-adrenal axis, measured indirectly through corticosterone secretion, was investigated in conscious rats. The mu- and delta-opioid receptor agonists Leu-enkephalinamide, morphine and beta-endorphin, given intracerebroventricularly, dose-dependently increased the serum corticosterone levels. The effect of Leu-enkephalinamide was not changed by pretreatment with the histamine H1- and H2-receptor antagonists mepyramine and cimetidine. When Leu-enkephalinamide, morphine and beta-endorphin were given 3 hr after compound 48/80, the serum corticosterone levels were higher than after either one of these drugs given separately, which suggests an independent mechanism of action. In rats pretreated 24 hr earlier with compound 48/80, i.e., when brain mast cells were completely degranulated, the stimulating effect of morphine was almost abolished and the effects of Leu-enkephalinamide and beta-endorphin were considerably reduced. Since the histamine levels in the whole brain and thalamus were elevated 3 and 24 hr after administration of compound 48/80, these results suggest that factors other than histamine depletion from brain mast cells by compound 48/80 may be responsible for the dramatic impairment of the stimulating effect of morphine, Leu-enkephalinamide and beta-endorphin on the pituitary-adrenal axis.
Turoń
M
M
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Chłap
Z
Z
Gadek-Michalska
A
A
Bugajski
J
J
Połczyńska-Konior
G
G
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000097:blood*; D004723:Endorphins / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D004723:Endorphins; D006633:Histamine Antagonists; D011957:Receptors, Opioid; D003189:p-Methoxy-N-methylphenethylamine; D009020:Morphine; D003345:Corticosterone