Alpha-fluoromethylhistidine decreases the Leu-enkephalinamide- and morphine-induced corticosterone response in rats.
The effect of inhibition of brain histamine synthesis by alpha-fluoromethylhistidine (alpha-FMH) on the pituitary adrenocortical activity stimulated by D-Ala-D-Leu-enkephalinamide (DADL) and morphine was investigated indirectly through corticosterone secretion in conscious rats. alpha-FMH (20 mg/kg i.p.) drastically reduced the whole brain histamine content, measured 2 h later. The same pretreatment also considerably reduced the corticosterone response to morphine given intraperitoneally. When alpha-FMH was administered intracerebroventricularly (50 micrograms), the maximum inhibition of the corticosterone response to DADL and morphine occurred 4 h after administration, which may suggest a weaker accessibility of alpha-FMH from the cerebral ventricle to the brain structures involved in pituitary-adrenocortical stimulation. The corticosterone responses were not related to the core temperature changes. These results indicate that inhibition of brain histamine synthesis by alpha-FMH considerably impairs the pituitary-adrenocortical response to the opioid delta- and mu-receptor agonists DADL and morphine. They also suggest that neuronal histamine is significantly involved in the central stimulation of the pituitary-adrenal axis by opioids.
Turon
M
M
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Fogel
W A
WA
Bugajski
J
J
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006640:Histidine Decarboxylase / Q000494:pharmacology*; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D008762:Methylhistidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine; C048614:enkephalinamide-Leu; D016308:Enkephalin, Leucine-2-Alanine; C030279:enkephalinamide-Leu, Ala(2)-; C028309:alpha-fluoromethylhistidine; D009020:Morphine; D006640:Histidine Decarboxylase; D003345:Corticosterone