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Biomedical subjects

C R Mantione

Publications and source records attributed to C R Mantione.

11 recordsLinked to original sources
PubMed1992

Reduced density of NMDA receptors and increased sensitivity to dizocilpine-induced learning impairment in aged rats.

About 20 min prior to training in a shock-motivated 14-unit T-maze, young (3-4 months) and aged (24-25 months) male Fischer-344 rats were given s.c. injections of either saline or dizocilpine (MK-801, 0.02 or 0.04 mg/kg), a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. The aged rats showed a dose-dependent impairment in maze performance. Deficiencies were manifested as increases in errors, in runtime from start to goal, and in the number and duration of shocks received. In contrast, young rats exhibited no detrimental effects of dizocilpine on maze performance. Analysis of [3H]glutamate binding in these rats revealed a marked age-related decline in NMDA receptor binding in hippocampus. A significant correlation was observed between errors in the maze and hippocampal [3H]-glutamate binding, but the correlation was positive, i.e., rats that made the most errors had the highest level of NMDA receptor binding. Thus, compared to young rats, aged rats were more sensitive to the behavioral effects of NMDA receptor antagonism and they showed a hippocampal loss of [3H]glutamate in binding, which may be related to the increased sensitivity to dizocilpine. The positive correlation between poor maze performance and NMDA receptor binding suggests that the behaviors assessed involve complex interactions between NMDA receptors and other neuronal systems in the hippocampus.

Aging↗
PubMed1990

A bradykinin (BK)1 receptor antagonist blocks capsaicin-induced ear inflammation in mice.

1. The effect of various peptide antagonists on capsaicin-induced (250 micrograms per ear) ear inflammation has been examined. 2. Co-administration of the substance P (SP) antagonist [D-Pro2,D-Trp7,9]SP at 100 and 300 micrograms per ear with capsaicin markedly attenuated oedema, whereas a vasopressin antagonist was ineffective. 3. Using the same scheme, the mixed BK2 and BK1 bradykinin (BK) antagonist NPC 567 (D-Arg[Hyp3,D-Phe7]BK) did not inhibit oedema at 100 micrograms per ear, but did inhibit at a higher dose (300 micrograms). The BK1 antagonist [Leu8,desArg9]BK produced significant inhibition at both doses. 4. When BK was used to induce ear inflammation (30 micrograms per ear), the SP antagonist inhibited ear oedema. Both BK receptor subtype antagonists inhibited inflammation with the BK1 being more potent than the BK2 antagonist. 5. These results suggest that BK1 along with BK2 receptors are located on capsaicin-sensitive fibres, where they may modulate the degree of neurogenic inflammation.

Animals↗
PubMed1989

Characterization of [3H]bradykinin binding sites in guinea-pig central nervous system: possible existence of B2 subtypes.

Specific [3H]bradykinin(BK) binding was investigated in membranes from guinea-pig brain. In kinetic experiments, specific [3H]BK binding (100 pM) reached equilibrium within 15 min at 25 degrees C (k + 1 = 1.40 nM-1min-1) and the binding was reversed by the addition of 1 microM BK (k-1 = 0.069 min-1). The presence of a high affinity BK binding site was also revealed in the guinea-pig brain by equilibrium saturation studies with a Kd value of 75 pM and a Bmax value of 4.9 +/- 0.9 fmol/mg protein. In inhibition experiments, the B2 antagonists (D-Phe7-BK and Thi5,8,D-Phe7-BK) inhibited [3H]BK binding, but not the B1 antagonist (des-Arg9[Leu8]-BK). D-Arg[Hyp3, D-Phe7]BK (B4801) showed a pseudo Hill coefficient of less than one. The KH and KL values are 1.8 and 94 nM. The regional distribution study shows the highest density of BK binding sites in the pons + medulla oblongata and the spinal cord, a moderate density in the cerebral cortex and hippocampus, and a low density in other brain regions. These data support the presence of B2 BK receptors in the guinea-pig brain and spinal cord and suggest the existence of B2 subtypes in the brain. The presence of these receptors suggests that BK acts as a neurotransmitter or a neuromodulator in these tissues.

Animals↗
PubMed1988

Purification and characterization of an endogenous protein modulator of radioligand binding to "peripheral-type" benzodiazepine receptors and dihydropyridine Ca2+-channel antagonist binding sites.

Acidified extracts of rat antral stomach chromatographed on octadecylsilane cartridges contained material that inhibited the binding of [3H]Ro 5-4864 (4'-chlorodiazepam) and [3H]nitrenidipine to "peripheral-type" benzodiazepine receptors and dihydropyridine Ca2+-channel antagonist binding sites respectively. This material reduced the apparent affinities of both radioligands without significantly affecting the maximum number of binding sites. In contrast, the binding of [3H]diazepam, [3H]Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a][1,4] benzodiazepine-3-carboxylate), and [3H]3-carbomethoxy-beta-carboline to "brain-type" benzodiazepine receptors and [3H]dihydroalprenolol binding to beta-adrenergic receptors were unaffected by this material. Subsequent column chromatography on hydroxylapatite purified this material by greater than 2000-fold. This semi-purified substance was resolved by reverse phase HPLC as one u.v. adsorbing peak that inhibited both [3H]Ro 5-4864 and [3H]nitrendipine binding. The activity of this 16,000 dalton substance was destroyed completely by both heat treatment and pronase and partially reduced by trypsin. Furthermore, the inhibitory activity of this substance was enhanced by Ca2+ in a concentration-dependent fashion (0.1 to 10 mM). Comparison of TLC scans of 2-9,10[3H]dipalmitoyl-phosphatidylcholine incubated with either the HPLC purified material or authentic phospholipase A2(PLA2) (Naja naja) revealed that this substance has enzymatic properties indistinguishable from PLA2. These findings suggest that this endogenous protein may be a PLA2 isoenzyme which may modify both "peripheral-type" benzodiazepine receptors and dihydropyridine Ca2+-channel antagonist binding sites.

Animals↗
PubMed1986

Sex differences in muscarinic receptor binding after chronic ethanol administration in the rat.

Male and female rats were administered ethanol (5% v/v) in a liquid diet for 18 weeks. Pair-fed control animals were fed the same diet except that dextrose was substituted isocalorically for ethanol. Normal controls received a commercial laboratory chow for the same duration. Results showed that, in females, chronic ingestion of an ethanol liquid diet significantly increased the number of muscarinic receptor binding sites compared to both control groups. In contrast, for males, there was no significant difference in the mean number of binding sites among the treatment groups. Furthermore, the mean maximum number of binding sites for males and females varied across brain areas. Males had a significantly greater number of receptor binding sites than females in the striatum, while females had a greater number in the cortex. It was suggested that the geuder differences observed in the present study could be mediated by hormonal effects on central muscarinic functioning.

Alcoholism↗
PubMed1985

Late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines.

Four classes of non-mammalian vertebrates were examined for the presence of both 'brain-specific' and 'peripheral-type' binding sites for benzodiazepines in the central nervous system. 'Brain-specific' binding sites for benzodiazepines were found in the central nervous systems of all non-mammalian vertebrates studied. However, in contrast to mammals, either very low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines were observed in the central nervous systems of these non-mammalian vertebrates. Furthermore, the density of 'peripheral-type' binding sites for benzodiazepines in non-mammalian vertebrate heart was less than or equal to 2% of that found in mammalian cardiac tissue. These findings suggest a very late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines, implying that these sites may have (a) highly specialized function(s) in both peripheral tissues and the central nervous system.

Animals↗
PubMed1985

Endogenous inhibitors of [3H] Ro 5-4864 binding to "peripheral-type" binding sites for benzodiazepines are present in peripheral tissues and brain.

Recent observations have shown that "peripheral-type" binding sites for benzodiazepines (PBS) are under neural and/or hormonal control in the pineal gland, olfactory bulb, and kidney. These studies resulted in a search for endogenous substances which might physiologically subserve PBS. Acidified methanol or trichloroacetic acid extraction of both peripheral tissues and brain followed by ultrafiltration and/or gel filtration and high performance liquid chromatography revealed the presence of both high (Mr greater than 10,000) and low (Mr less than 500) molecular weight substances which inhibit the binding of [3H] Ro 5-4864 to PBS while only slightly inhibiting the binding of [3H] diazepam to classical "brain-type" benzodiazepine receptors.

Animals↗
PubMedDate not supplied

Identification of B2 bradykinin binding sites in the guinea pig nasal turbinate.

Specific high affinity BK binding sites in the nasal turbinate of the guinea pig have been demonstrated. Specific [3H]BK binding (10-330 pM) was saturable, and nonlinear least squares analysis indicated the presence of a high affinity binding site with a Kd value of 60 (50-78) pM and a Bmax value of 13.1 = 2.0 fmol/mg protein. In inhibition experiments, D-Phe7-BK (a B2 antagonist) inhibited [3H]BK binding with a Ki value of 23 nM, while des-Arg9[Leu8]-BK (a B1 antagonist) had no effect up to a concentration of 10 microM. These studies indicate the presence of B2 BK receptors in the guinea pig nasal turbinate.

Animals↗