Angela Santagostino

Lack of opiate receptor involvement in centrally induced calcitonin analgesia

Abstract Calcitonin (CT) injected into the brain ventricles (ICV) of conscious rabbits induced an analgesia not reversable by naloxone which could be repeatedly elicited (for 5 days), while tolerance to morphine developed. CT and morphine synergized in vivo when administered ICV in combination. CT did not alter electrically-induced contractions of guinea-pig myenteric plexus-longitudinal muscle and no displace of 3 H-dihydromorphine by CT was observed in brain opiate receptor preparations. We have concluded that the mechanism of centrally induced CT analgesia may be opiate-independent.

Vulnerability of mitochondrial complex I in PC12 cells exposed to manganese.

The present findings provide experimental evidence for the hypothesis that an impairment of mitochondrial function may be involved in manganese neurotoxicity. Specifically, the treatment of dopaminergic neuronal-derived cell line (PC12) with MnCl2 produced a significant inhibition of some mitochondrial complexes of the respiratory chain, while in the glial-derived cell line (C6) this effect was not observed. In PC12 the decrease in complex I activity was more pronounce than in other mitochondrial complexes. However treatment of cells with ZnSO4 exerted no significant variations in enzymatic activities. A direct exposure of mitochondrial fraction to MnCl2 reduced enzymatic activities of mitochondria in both cell lines adding further support to the proposed theory that the different sensitivity of the cells to manganese may be explained by a difference in uptake or intracellular storage. These data indicate that manganese neurotoxicity could be the result of a direct effect just on complex I activity or due to a secondary effect of oxidative stress induced by an excess of this transition metal.

Leu-enkephalin-stimulated growth hormone and prolactin release in the rat: comparison with the effect of morphine.

The effect of Leu5-enkephalin on growth hormone (GH) and prolactin (PRL) release was studied in vivo in the infant rat and compared to that of morphine. In 10 day-old pups, intracerebroventricular injection of Leu5-enkephalin (50, 75 and 100 μg) resulted in a dose-related increase in plasma GH; morphine was active as GH releaser at the dose of 5 and 10 μg, but not at 2.5 μg. Pretreatment with naloxone (2 mg/kg ip) suppressed the GH-releasing effect of either Leu5-enkephalin (100 μg) or morphine (10 μg). Leu5-enkephalin (75 and 100 μg) induced a rise in plasma PRL which was neither dose-related nor antagonized by naloxone; morphine (5 and 10 μg) was active as PRL releaser and its effect was antagonized by naloxone. These results indicate that: 1) Leu5-enkephalin stimulates both GH and PRL release; 2) the release of GH by Leu5-enkephalin but likely not that of PRL involves specific opiate receptors; 3) morphine releases GH and PRL through specific opiate receptors.

Metal biomonitoring with mosses in the surroundings of an oil-fired power plant in Italy.

Levels of 12 trace elements were measured in samples of the bryophyte Hypnum cupressiforme Hedw. and in soil collected in the surroundings of an oil-fired power plant in Northern Italy. Metal bioaccumulation in moss was estimated after soil correction in order to obtain deposition patterns and individuate potentially toxic metals emitted from the plant. V and Ni, occurring together in fuel oil, showed highest bioaccumulation values near the stacks. Mean contamination of the study area for these elements is 5.5 (V) and 3.3 (Ni) times the background levels of the reference site. Other elements showed only limited alterations of bioaccumulation values, in relation to agricultural and industrial activity in the study area.

Effects of met-enkephalin on body temperature of normal and morphine-tolerant rats

The endogenous opioid met-enkephalin intraventricularly administered to the rat at the dose of 100 μg raised rectal temperature, whereas 400 μg of the pentapeptide caused a diphasic effect, i.e., hypothermia followed by hyperthermia. Met-enkephalin was ineffective when administered i.p. The effects on temperature were substantially similar to those elicited, for both routes of administration, by morphine, which may either raise or lower rat temperature depending on the dose. More naloxone was required to antagonize thermic effects of met-enkephalin than morphine. Finally, there was a lack of effects on temperature for metenkephalin centrally administeted to morphine-tolerant animals, thus providing further evidence, in vivo, of cross tolerance between opiates and naturally occurring ligands of opiate receptors.

Decreased antinociceptive effect of morphine in rats treated intraventricularly with prostaglandin E1

The administration of prostaglandin E1 intracerebrally through a cannula implanted in a lateral ventricle, antagonizes morphine analgesia in rats.An electrical stimulation technique was adopted on the rats tail to measure the antinociceptive activity of morphine. Some hypotheses are advanced in order to explain the sensitizing activity of prostaglandin E1.

Benomyl affects the microtubule cytoskeleton and the glutathione level of mammalian primary cultured hepatocytes.

Rat primary hepatocyte cultures have been used to study the effect of Benomyl alone or in combination with Pirimiphos-methyl. The results presented demonstrate that Benomyl alone is responsible for the microtubular disorganization in both a time- and dose-dependent manner, that the effect is reversible after the agent is removed, and that Benomyl is a potent glutathione-depleting agent. Pirimiphos-methyl, alone or combined with Benomyl had no effect on microtubule organization, but reinforced the decrease in glutathione.

Cold stress in the rat induces parallel changes in plasma and pituitary levels of endorphin and ACTH

Endorphin and ACTH-like materials levels in rat plasma and pituitary were measured by radioimmunoassay under baseline and cold stress conditions. Cold stress significantly increased plasma beta-endorphin and ACTH immunoreactivity. A rise in these two peptides was also found in the neurointermediate lobe of the pituitary, while in the anterior lobe their levels were unaffected. These findings suggest that the rise of beta-endorphin and ACTH content in the neurointermediate lobe occurs as a compensatory biosynthetic mechanism for the peptides released from the adenohypophysis.

Interactions of manganese with human brain glutathione-S-transferase

Chronic exposure to manganese-laden dusts induces, in humans and lower primates, neurological disorders with clinicopathological features that resemble idiopathic Parkinsons disease. As many authors have suggested, manganese neurotoxicity could be related to the capability of this metal to increase catechol autoxidation in catecholaminergic neurons, therefore increasing the formation of toxic compounds such as peroxides, superoxides, free radicals, and semi-orthoquinones. Oxidative stresses and consequent neuronal damage could then occur if physiological scavenger mechanisms fail in their detoxifying action. We here report that manganese chloride weakly inhibits, in a dose-dependent way by a reversible competitive mechanism, human brain glutathione-S-transferases possibly suggesting that manganese intoxication could cause intraneuronal accumulation of cytotoxic compounds. We also report that both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin known to induce in man Parkinson-like syndromes, and one of its metabolites 1-methyl-4-phenylpyridinium failed to decrease glutathione-S-transferase activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) affects the actin cytoskeleton and calcium level of Swiss 3T3 mouse fibroblasts

Organization of the actin cytoskeleton, the cytosolic free-calcium concentrations and ATP levels were analyzed in 3T3 mouse fibroblasts treated with 0.75 or 1.5 mM MPTP. In the presence of the drug actin filaments were time- and dose-dependently disorganized, ATP level was unaffected and intracellular calcium increased within 5 s. The correlation between MPTP cytotoxicity and [Ca2+]i level emerging from these results, suggests that the primary effect of the molecule itself is on the plasma membranes integrity for calcium ion regulation.