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Biomedical subjects

A Capasso

Publications and source records attributed to A Capasso.

At least 55 records · Page 3Linked to original sources
PubMed1997

Arachidonic acid and its metabolites are involved in the expression of morphine dependence in guinea-pig isolated ileum.

The effects of phospholipase A2, cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase inhibitors were investigated on the naloxone-precipitated withdrawal contracture of the acute morphine-dependent guinea-pig ileum in vitro. Mepacrine (a phospholipase A2 inhibitor), tolmetin (selective cyclooxygenase-1 inhibitor) and meloxicam (selective cyclooxygenase-2 inhibitor) treatment before or after morphine was able to both prevent and reverse the naloxone-induced contracture after exposure to morphine in a concentration-dependent fashion. Also, nordihydroguaiaretic acid (5-lipooxygenase inhibitor) was able to block the naloxone-induced contracture following exposure to morphine when injected before or after the opioid agonist. The results of the present study suggest that arachidonic acid and its metabolites (prostaglandins and leukotrienes) are involved in the development of opioid withdrawal.

Animals↗
PubMed1997

Difference in hepatic metallothionein content in Antarctic red-blooded and haemoglobinless fish: undetectable metallothionein levels in haemoglobinless fish is accompanied by accumulation of untranslated metallothionein mRNA.

Icefish (family Channichthyidae, suborder Nothothenioidei) are a group of Antarctic fish that have evolved unique phenotypes in order to adapt to the environment in which they live. Besides the lack of haemoglobin and the drastic reduction in the number of erythrocyte-like cells, another striking feature of the icefish is that their liver is devoid of metallothionein. These cysteine-rich heavy-metal-binding proteins are usually present in large amounts in a large variety of organisms, from bacteria to mammals. Despite the failure to detect appreciable levels of metallothionein in icefish liver, a cDNA encoding metallothionein was produced from total RNA by reverse transcriptase PCR. The icefish metallothionein showed high percentage identity with metallothionein from Trematomus bernachii, a red-blooded Antarctic fish in which a normal content of hepatic metallothionein was found. Steady-state mRNA levels were assessed in fish liver by high-stringency hybridization of the metallothionein probe with total RNA. The results showed that icefish livers retain large amounts of untranslated metallothionein mRNA. The stability of the icefish transcript might be correlated with the lack of specific motifs in the untranslated 3' ends of mRNA.

Adaptation, Physiological↗
PubMed1997

PCR amplification and cloning of metallothionein complementary DNAs in temperate and Antarctic sea urchin characterized by a large difference in egg metallothionein content.

Metallothionein levels were determined in the eggs of two sea urchin species, the Mediterranean Sphaerechinus granularis and the Antarctic Sterechinus neumayeri. While appreciable levels of metallothionein were found in S. granularis eggs, a negligible amount was detected in S. neumayeri. Two metallothionein isoforms were purified from S. granularis, and metallothionein cDNAs were obtained by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Two distinct cDNA species were cloned and sequenced. The translated amino acid sequences of these two forms consisted of 67 residues and differed in two amino acid substitutions. Despite the lack of metallothionein in S. neumayeri eggs, a metallothionein cDNA was obtained by RT-PCR amplification and a single amino acid sequence coding for a 63 residues MT was deduced. A comparative analysis of the primary structure of S. granularis and S. neumayeri metallothioneins with those of the other sea urchin metallothioneins has been performed. Sea urchin metallothioneins appear to be less similar to each other than metallothioneins of closely related vertebrates.

Amino Acid Sequence↗
PubMed1997

Dexamethasone inhibition of acute opioid physical dependence in vitro is reverted by anti-lipocortin-1 and mimicked by anti-type II extracellular PLA2 antibodies.

Dexamethasone has been shown to inhibit opiate withdrawal, in an in vitro model. In this respect, we suggested that dexamethasone could reduce opiate withdrawal by blocking the release of prostaglandins' precursor, arachidonic acid through protein synthesis dependent-mechanisms (1). Since arachidonic acid is released by the enzyme phospholipase A2 (PLA2) in the present paper we evaluate whether dexamethasone effect may by related to inhibition of PLA2 activity. Therefore, the effect of a neutralizing anti-lipocortin-1 antibody and a polyclonal anti-type II extracellular phospholipase A2 antibody on the opiate withdrawal in vitro was considered. Following a 4 min in vitro exposure to morphine a strong contracture of guinea-pig isolated ileum was observed after the addition of naloxone. Dexamethasone at concentration of 5x10(-5) M reduces of 50% morphine withdrawal and the polyclonal anti-type II extracellular PLA2 antibody (in a dilution 1:1000) mimicked dexamethasone inhibitory effect. Incubation of the ileum preparation with a neutralizing anti-lipocortin-1 antibody (at a dilution of 1:10.000) 30 min before dexamethasone reverted the steroid effects. These results suggest that dexamethasone inhibition of opiate withdrawal is due to extracellular type II PLA2 inhibition through lipocortin-1.

Animals↗
PubMed1997

GABAA receptor antagonists reduce acute opiate withdrawal in isolated tissue.

1. The effect exerted by GABAA receptor agonists and antagonists on the acute opiate withdrawal induced by mu and k receptor agonists were investigated in vitro. 2. Following a 4 min in vitro exposure to morphine (less selective mu agonist), DAGO (highly selective mu agonist) and U50-488H (highly selective k agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3. Bicuculline (1 x 10(-5)-5 x 10(-5)-1 x 10(-4) M), a GABAA receptor antagonist, injected 10 min before or after the opioid agonists was able dose-dependently to antagonize the naloxone-induced contracture after exposure to mu (morphine and DAGO) and k (U50-488H) opiate agonists. 4. Furthermore, picrotoxin (1 x 10(-5)-5 x 10(-5)-1 x 10(-4) M), an antagonist of GABA-linked chloride channels, was able to exert the same effects. 5. Muscimol (1 x 10(-5)-5 x 10(-5)-1 x 10(-4) M), a GABAA receptor agonist, was able to increase dose dependently both mu and k opiate withdrawal. 6. The data indicate that both GABAA receptor agonists and antagonists are able to control opiate withdrawal in vitro suggesting an important functional interaction between GABAergic system and the opioid withdrawal both at the mu and k receptor level.

Animals↗
PubMed1997

Anticonvulsive activity of a new GABA mimetic drug.

This study examines the pharmacological profile of a new GABA mimetic drug, 4-[(2H)-1,3-benzoxazine-2,4(3H)-dione]-butyric acid (BXDBA), using both a behavioral and an anticonvulsive study. The behavior elements considered were locomotor activity, motor coordination, catalepsy, behavior and antinociception. The anticonvulsive study was performed using the convulsive agent bicuculline. BXDBA [10, 20 and 40 mg/kg, intraperitoneally (i.p.)] did not significantly modify animal behavior or the nociceptive threshold of the animals. The anticonvulsive study indicated that BXDBA (10, 20 and 40 mg/kg, i.p.), injected 60 min before bicuculline (10 micrograms/intracerebroventricular (i.c.v.)/mouse) induced a dose-dependent and significant reduction of the convulsive activity of bicuculline whereas it was ineffective if injected immediately before the convulsive agent. Our data indicate that this new GABA mimetic drug possesses good anticonvulsive activity and its ability to block bicuculline-induced convulsions suggests that it could be a GABAA mimetic drug. Furthermore, since BXDBA is able to act after systemic administration, our data suggest that this new GABA mimetic drug crosses the blood-brain barrier.

Analgesics↗
PubMed1997

New protopine and benzyltetrahydroprotoberberine alkaloids from Aristolochia constricta and their activity on isolated guinea-pig ileum.

Five new protopine-type alkaloids, 3,5-di-O-methylconstrictosine (1), 5,6-dihydro-3,5-di-O-methylconstrictosine (2), 5,6-dihydroconstrictosine (3), constrictosine (4), 3-O-methylconstrictosine (5), and a novel 8-benzylberberine-type alkaloid, (-)-8 beta-(4'-hydroxybenzyl)-2,3-dimethoxyberbin-10-ol (6) were isolated from the aerial parts of Aristolochia constricta. Their structures were elucidated by physical and spectroscopic data. The results of our pharmacological experiments indicated that MeOH extract, its partially purified fraction VI and the protopine derivatives constrictosine 1-5, significantly reduced, in a dose dependent manner, the electrical, acetylcholine, and histamine contractions of the isolated guinea-pig ileum.

Acetylcholine↗
PubMed1997

Differential influence of D1 and D2 dopamine receptors on acute opiate withdrawal in guinea-pig isolated ileum.

1. The effects exerted by D1 and D2 dopamine agonists and antagonists on the acute opiate withdrawal induced by mu- and kappa-receptor agonists were investigated in vitro. 2. Following a 4 min in vitro exposure to morphine (moderately selective mu-agonist), [D-Ala2, Me-Phe4, Gly-ol5]enkephalin (DAMGO, highly selective mu-agonist) or U-50488H (highly selective kappa-agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3. The non-selective dopamine receptor antagonist haloperidol when added before or after the opioid agonists, was able dose-dependently to prevent or to reverse the naloxone-induced contracture after exposure to mu- (morphine and DAMGO) and kappa- (U-50488H) opioid agonists. The non-selective dopamine receptor agonist, apomorphine, was able to exert the same effects only at the highest concentration used. 4. The selective D2 dopamine receptor antagonist, sulpiride, was also able to reduce dose-dependently both mu- and kappa-opioid withdrawal, whereas the D1-receptor selective antagonist SCH 23390 did not affect either mu- or kappa-opioid withdrawal. 5. Bromocriptine, a D2 selective dopamine receptor agonist was able to increase significantly, and in a concentration-dependent manner, the naloxone-induced contracture by mu- and kappa-opioid agonists, whereas SKF 38393, a D1 selective dopamine receptor agonist, increased only the withdrawal after morphine or U50-488H. 6. Our data indicate that both D1 and D2 dopamine agonists and antagonists are able to influence opiate withdrawal in vitro, suggesting an important functional interaction between the dopaminergic system and opioid withdrawal at both the mu- and kappa-receptor level. 7. Furthermore, the ability of sulpiride to block strongly opiate withdrawal when compared to SCH 23390, as well as the effect of bromocriptine to increase opiate withdrawal suggest that D2 dopamine receptors may be primarily involved in the control of opiate withdrawal.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1997

Isoquinoline alkaloids from Argemone mexicana reduce morphine withdrawal in guinea pig isolated ileum.

The present study examined the effect of the MeOH extract, partially purified fraction (IV), and pure compounds from Argemone mexicana L. (Papaveraceae) on the morphine withdrawal in guinea pig isolated ileum. The MeOH extract, the partially purified fraction (IV), and the pure compounds isolated from A. mexicana significantly and in a concentration-dependent manner reduced the morphine withdrawal. Since the pure compounds were identified as protopine and allocryptopine, the observed effects could be related to these compounds. The results of the present study suggest that isoquinoline alkaloids may be potential agents in the treatment of drug abuse.

Alkaloids↗
PubMed1997

Indole alkaloids from Sickingia williamsii reduce the in-vitro effects of morphine withdrawal in the guinea-pig.

The effect of indole alkaloids from Sickingia williamsii Standl. (Rubiaceae) on the effects of morphine withdrawal have been examined in-vitro. All the indole alkaloids isolated from S. williamsii (10(-4), 5 x 10(-5) and 10(-5) M) significantly and in a concentration-dependent manner reduced the effects of morphine withdrawal on the guinea-pig ileum. The results suggest that these alkaloids might be potential anti-addictive agents.

Acetylcholine↗
PubMed1997

Synthesis, stability and anticonvulsant activity of two new GABA prodrugs.

4-(3,4-Dihydro-2,4-dioxo-2H-1,3-benzoxazin-3-yl)-butyric acid (7) and its ester 6, two potential gamma-aminobutyric acid (GABA) prodrugs, were synthesized and studied to determine their stability in aqueous buffer and their susceptibility to undergo enzymatic hydrolysis in vitro (mouse plasma). Both compounds were fairly stable in aqueous media, (t1/2 = 68.2 h and 25.7 h, respectively). The 3,4-dihydro-2,4-dioxo-2H-1,3-benzoxazine ring underwent enzymatic hydrolysis (t1/2 = 5.8 h) in compound 7, whereas in compound 6 it seemed not to be opened by mouse plasma esterases within the observation time (3h). Both compounds were tested for their anticonvulsant activity in pentetrazole (PTZ) treated mice, and showed significant activity. Compound 7, administered as sodium salt 8, was active at relatively low doses and can be considered a very interesting GABA prodrug.

Animals↗
PubMed1997

Experimental animal studies on the hypoglycemic effects of a Copalchi extract.

The hypoglycemic effect of a Copalchi extract (Sucontral) was tested in 60 adult-male and female-Wistar rats in the present randomized, placebo-controlled, parallel-comparative animal study. A control group receiving only an Altromin standard chow was compared to treatment groups which received an Altromin chow enriched with Copalchi dry substance at 0.028% m/m or at 0.28% m/m. The study period was 30 days. The distinctly significant blood glucose lowering effect of the Copalchi extract could be demonstrated in both treatment groups. No significant difference in the antidiabetic effect was seen between the two concentrations. The onset of action of the Copalchi extract was observed between treatment day 1 and 3. A 20-25% decrease in the blood glucose concentration was achieved between the 7th and 15th day of treatment and remained at this level thereafter. This plateau was reached in the female rats already between treatment day 3 and 5. The parallel observed increase in the mean body weight was not striking and generally was the same between the test animals and the control animals.

Animals↗
PubMed1996

Subcellular distribution of "intersecting' beta-N-acetylglucosaminyltransferase in Dictyostelium discoideum. A likely marker for the Golgi apparatus.

Glycoprotein processing in Dictyostelium discoideum is characterized by enzyme catalyzed steps not reported in other organisms. One of these is the formation of a beta 1 --> 4 linkage between GlcNAc and the mannose linked to the core mannose in the alpha 1 --> 6 position of N-glycosides. A simple and sensitive assay for this GlcNAc transferase activity, using a tri-mannose acceptor and a low concentration of UDP-GlcNAc, was developed. Homogenates of the organism were subjected to sub-cellular fractionation by centrifugation in discontinuous sucrose gradients. The specific activity was enriched 4-5-fold in a crude membrane fraction. The transferase was purified 10-12-fold in a membrane fraction that bands on top of 1.1 M sucrose. This fraction was also enriched in nucleotidyldiphosphatase. The enriched fraction was deficient in glucose-6-phosphatase, an endoplasmic reticulum marker. Approx. 80% of the transferase activity was latent, and unavailable to protease. Purified membranes were either subjected to phase separation in Triton X-114, or sodium carbonate extraction or sonication. In each case, the transferase behaved as an intrinsic membrane protein. Several secreted and lysosomal proteins are modified by the enzyme. These data support the idea that the GlcNAc transferase is present as an integral Golgi membrane protein and that at least the catalytic center of the transferase is on the lumenal side of the vesicles.

Acid Anhydride Hydrolases↗
PubMed1996

Opioid receptor selectivity alteration by single residue replacement: synthesis and activity profile of [Dmt1]deltorphin B.

The single amino acid replacement of 2',6'-dimethyl-L-tyrosine in deltorphin B (H-Dmt-D-Ala-Phe-Glu-Val-Val-Gly-NH2) yielded high affinity for mu- and delta-binding sites. [Dmt1]Deltorphin B lacks activity at kappa-opioid binding sites. Bioactivity in vitro with guinea-pig ileum confirmed that [Dmt1]deltorphin B interacted with mu-opioid receptors by reducing electrically induced contractions in a naloxone-reversible manner and was 150-fold more potent than morphine and comparable to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO). The inhibition of spontaneous contractions of rabbit jejunum provided evidence for delta-opioid receptor interaction. Analgesia (hot plate and tail flick tests) revealed that [Dmt1]deltorphin B was 180- to 200-fold more potent than morphine. Pretreatment with naloxone, naltrindole or H-Dmt-Tic-Ala-OH (a highly selective delta-opioid receptor antagonist) prevented [Dmt1]deltorphin B antinociception. Thus, [Dmt1]deltorphin B exhibited remarkably high dual affinity and bioactivity toward delta- and mu-opioid receptors.

Animals↗
PubMed1996

Dmt-Tic-OH a highly selective and potent delta-opioid dipeptide receptor antagonist after systemic administration in the mouse.

Dmt-Tic-OH (DTOH) and Dmt-Tic-Ala-OH (DTAOH), effective antagonists in vitro, represent a new potent opioid dipeptides for the delta-opioid receptor (Ki delta of 0.022 nM and a selectivity, Ki mu/Ki delta, of 150,000 for DTOH; Ki delta of 0.285 nM and a selectivity Ki mu/Ki delta, of 20,4 for DTAOH). In the present study we considered the pharmacological activity of these two new delta opioid peptide receptor antagonists in vivo. Therefore, we have evaluated their possible antagonistic activity against the antinociception induced by the highly selective delta opioid receptor agonist, [D-Ala2]deltorphin II (DEL). Furthermore, these two delta opioid peptide receptor antagonists were injected centrally or peripherally in order to assess their ability to act also after systemic administration. Concurrent i.c.v. injection of DTOH or DTAOH (0.5-1.0-2.0 nM) with DEL (5 nmol) induced a significant reduction of DEL antinociception. By contrast, while DTOH (10-20-40 mg/kg) administered peripherally (i.p., s.c. or i.v.) was also able to reduce DEL antinociception, DTAOH failed. The present results indicate that DTOH is the first opioid dipeptide with delta antagonist activity after systemic administration and it could be important in the clinical and therapeutic applications.

Animals↗
PubMed1996

Actinomycin D blocks the reducing effect of dexamethasone on amphetamine and cocaine hypermotility in mice.

1. The present study examined a time-course effect of dexamethasone (DEX) on amphetamine and cocaine-induced hypermotility in mice and the influence of actinomycin D (dactinomycin), a protein synthesis inhibitor, on DEX effects. 2. Amphetamine (5 mg/kg IP) and cocaine (10 mg/kg IP) increased markedly the locomotor activity of mice, whereas DEX alone (0.1-1.0-10 mg/kg IP) did not modify the activity of control mice. 3. DEX pretreatment 0, 15, 30, 60 and 120 min before amphetamine or cocaine strongly decreased both amphetamine and cocaine effects, but no dose-related effect was observed. 4. The time-course study performed with DEX revealed differences in its reducing effect on cocaine and amphetamine hypermotility when the groups of animals treated with the steroid immediately before the cocaine (or amphetamine) injection were compared to those treated with the steroid later (15, 30, 60 and 120 min). 5. Furthermore, actinomycin D was able to block the reducing effect of DEX on both amphetamine and cocaine hypermotility. 6. Therefore, considering that the administration time of the steroid seems to be an important factor for reducing both cocaine and amphetamine hypermotility, and actinomycin D was able to block the reducing effect of the steroid, our study suggests that DEX exerts its reducing effect through a genomic activation.

Amphetamine↗
PubMed1996

Dexamethasone modifies the behavioral effects induced by clonidine in mice.

The present study examines the influence of dexamethasone on behavioral effects induced by clonidine in mice. 2. The behavior elements considered were locomoter activity, rota rod, catalepsy and stereotyped behavior (rearing, grooming, social response test, crossing, smelling, washing face, scratching and bar holding). 3. Clonidine (0.1-0.5-1.0 mg/kg, IP) induced a significant reduction of all behavioral elements studied when compared to the saline treated group: the behavioral reduction was significant 10 min after administration and lasted for the entire recording period (120 min). 4. Dexamethasone (0.1-0.5-1.0 mg/kg, IP) per se did not induce significant changes in the behavior elements recorded. 5. Dexamethasone (0.1-0.5 mg/kg, IP) dod not affect behavioral effects induced by the 3 doses of clonidine, whereas the high dose (1 mg/kg) of the steroid significantly reduced its behavioral inhibition. 6. The results of the present study suggest that dexamethasone induces significant effects on clonidine-induced behavioral effects and that this may be related to an interference with the monoaminergic system.

Animals↗