Arginine vasopressin antinociception in the rat nucleus raphe magnus is involved in the endogenous opiate peptide and serotonin system.

Arginine vasopressin (AVP) in the nucleus raphe magnus (NRM) has been implicated in antinociception. This communication was designed to investigate which neuropeptide and neurotransmitter are involved in AVP antinociception in the rat NRM. The results showed that (1) in the NRM perfuse liquid, pain stimulation could increase the concentrations of AVP, leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), beta-endorphin (beta-Ep), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), but not change the concentrations of dynorphinA(1-13) (DynA(1-13)), oxytocin, achetylcholine, choline, gamma-aminobutyric acid, glutamate, dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, norepinephrine and epinephrine; (2) in the NRM perfuse liquid, AVP increased the concentrations of L-Ek, M-Ek, beta-Ep, DynA(1-13), 5-HT and 5-HIAA, but did not change the concentrations of oxytocin and the other studied neurotransmitters; (3) AVP antinociception in the NRM was attenuated by cypoheptadine (a 5-HT-receptor antagonist) or naloxone (an opiate receptor antagonist), but was not influenced by the other studied receptor antagonists. The data suggested that AVP antinociception in the NRM might be involved in endogenous opiate peptide and 5-HT system.

Endogenous opiate peptides in the spinal cord are involved in the analgesia of hypothalamic paraventricular nucleus in the rat.

Many studies have shown that hypothalamic paraventricular nucleus (PVN) plays a role in pain process, and endogenous opiate peptide system in the spinal cord is involved in nociception. This communication was designed to study the relationship between PVN and endogenous opiate system in the spinal cord in the rat. The results showed that in both the thoracic and the lumber spinal cord, microinjection of 100 ng L-glutamate sodium into PVN could increase leucine-enkephalin (L-Ek), beta-endorphin (beta-Ep), dynorphinA(1-13) (DynA(1-13)) concentrations and PVN cauterization decreased L-Ek and beta-Ep concentrations. Pretreatment of the spinal cord with 5 microg naloxone, an opiate receptor antagonist could partly reverse the analgesia induced by microinjection of 100 ng L-glutamate sodium into PVN. The data suggested that PVN analgesia might be involved in the endogenous opiate peptide system in the spinal cord independently.

Separation, identification of uremic middle molecules, and preliminary study on their toxicity.

BACKGROUND: Compounds accumulating in uremic serum with molecular mass from 300 to 5000 Da are called uremic middle molecules (UMMs). In our previous work, two UMM fractions A and B were obtained from uremic sera, urine, and normal urine by gel permeation chromatography (GPC), and six UMMs from subfraction A3 of uremic plasma and normal urine were purified and characterized. METHODS: Urine and serum samples from uremic patients and healthy subjects were isolated by GPC, ion exchange chromatography (IEC), and reversed-phase high-performance liquid chromatography (RP-HPLC). Moreover, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) were used to characterize the compounds. The effects of subfraction A3 on renal function were studied in rabbit models with chronic renal failure (CRF). RESULTS: A compound with molecular weight 1007.94 in subfraction A3 was determined to be an octapeptide by mass spectrometry, with an amino acid sequence of Val-Val-Arg-Gly-Cys-Thr-Trp-Trp. Two CRF rabbits injected with A3 died in 5 days, while the other two CRF rabbits (no injection) survived a few days. By multistep chromatography and MALDI-TOF MS, another 11 endogenous compounds were found not only in the subfraction B9 of uremic sera but also in that of normal urine. CONCLUSION: Seventeen endogenous middle molecular compounds were found in fractions A and B of uremic plasma and normal urine, among them an octapeptide with M(W) 1007.94 in subfraction A3. Preliminary experimental results on rabbits indicate that subfraction A3 could accelerate the death of rabbits with CRF.