enkephalin--leucine-2-alanine and alpha-fluoromethylhistidine

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.

Topics: Animals; Body Temperature; Brain; Corticosterone; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Histamine Release; Histidine Decarboxylase; Male; Methylhistidines; Morphine; Pituitary-Adrenal System; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu

The effects of i.c.v. injected selective ligands for mu and delta opioid receptors on histamine (HA) turnover in the mouse brain were investigated to determine the receptor subclasses involved in the neurochemical response to opioids. HA turnover was measured by the accumulation of tele-methylhistamine, a major metabolite of brain HA, after pargyline injection (65 mg/kg i.p.). The increase in the HA turnover induced by [D-Ala2,D-Leu5] enkephalin (0.5 microgram i.c.v.) was antagonized by naloxone (0.3 microgram i.c.v.) but not by ICI 174,864 (5 micrograms i.c.v.), a selective delta receptor antagonist. [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO; 0.1-0.5 microgram i.c.v.), a selective mu receptor agonist, produced an increase in the HA turnover, whereas [D-Thr2-Leu5]enkephalin, Thr (0.1-1.0 microgram i.c.v.), a selective delta receptor agonist, had little effect on the HA turnover. DAGO (0.1 microgram i.c.v.) also increased the steady-state level of tele-methylhistamine but not that of HA. The effect of DAGO was observed in various brain regions except for the hypothalamus, and it was the most marked in the striatum. DAGO (10(-7) and 10(-6) M) significantly increased the K+ (30 mM)-evoked HA release from mouse cerebral cortical slices without influencing on the spontaneous HA release. The enhancement of HA release induced by DAGO (10(-6) M) was blocked completely by naloxone (10(-6) M) but not by tetrodotoxin (10(-6) M). These results suggest that opioids with mu agonist activity increase brain HA turnover by facilitating HA release from nerve endings.

Topics: Animals; Brain; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Histamine; Male; Methylhistamines; Methylhistidines; Mice; Naloxone; Oligopeptides; Receptors, Opioid; Receptors, Opioid, mu; Tetrodotoxin

When the histamine (HA) turnover in the brain of mice was estimated on the basis of the pargyline-induced accumulation of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, the enhancing effect of phencyclidine (PCP) on the HA turnover was antagonized by a large dose of naloxone. However, a dopamine receptor antagonist haloperidol, which is also a potent sigma receptor antagonist, did not inhibit the effect of PCP on the HA turnover. [D-Ala2,D-Leu5]enkephalin, a prototypic delta opioid agonist, markedly enhanced the HA turnover. The effect of this peptide was demonstrated not only when the HA turnover was determined by the pargyline-induced t-MH accumulation but when it was estimated by the HA depletion induced by alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. A sigma agonist, SKF-10047, and a kappa agonist, ethylketazocine, had no PCP-like enhancing effect on the HA turnover. These results suggest that PCP enhances the brain HA turnover in mice by stimulating, probably indirectly, endogenous opioid systems.

Topics: Analgesics, Opioid; Animals; Brain; Cyclazocine; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Ethylketocyclazocine; Haloperidol; Histamine; Histidine Decarboxylase; Ketamine; Male; Methylhistidines; Mice; Naloxone; Pargyline; Phenazocine; Phencyclidine; Receptors, Opioid