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Biomedical subjects

I Marabese

Publications and source records attributed to I Marabese.

15 recordsLinked to original sources
PubMed2001

Metabotropic and NMDA glutamate receptors participate in the cannabinoid-induced antinociception.

The purpose of this study was to evaluate the possible contribution of metabotropic glutamate receptors (mGluRs) to cannabinoid-induced antinociception in the periaqueductal grey (PAG) matter of rats. Intra-PAG microinjection of WIN 55,212-2, a cannabinoid receptor agonist, increased the latency of the nociceptive reaction (NR) in a dose-dependent fashion in the plantar test. This effect was prevented by pretreatment with SR141716A, a selective antagonist of CB1 receptors. When injected alone, SR141716A produced, with the highest dosage used, a significant reduction in the latency of the NR. CPCCOEt, a selective mGlu1 receptor antagonist, was unable to prevent the analgesia produced by WIN 55,212-2. On the contrary, MPEP, a selective mGlu5 receptor antagonist, completely antagonized the effect of WIN 55,212-2. However, the analgesia induced by CHPG, a selective mGlu5 receptor agonist, was blocked by MPEP but not by SR141716A. When injected alone, CPCOOEt produced no effect, whereas MPEP produced, with the highest dosage used, a significant reduction in the latency of the NR. These data emphasize that mGlu5 receptors, but not mGluR1, may modulate nociception in the PAG. Similarly, a pretreatment with either 2-(S)-alpha-EGlu or (RS)-alpha-MSOP, selective antagonists for group II and III mGluRs, respectively, prevented the WIN 55,212-2-induced analgesia. When the higher dosage of (RS)-alpha-MSOP was used a decrease in the latency of the NR was observed. This was not the case for 2-(S)-alpha-EGlu. Pretreatment with DL-AP5, a selective antagonist of N-methyl-D-aspartate (NMDA) receptors, blocked the effect of WIN 55,212-2, and by increasing the dosage strongly reduced per se the latency of the NR. This study suggests that endogenous glutamate could tonically modulate nociception through mGlu and NMDA receptors in the PAG matter. In particular, the physiological stimulation of these receptors seems to be required for the cannabinoid-induced analgesia in this midbrain area.

Analgesics↗
PubMed2000

Periaqueductal gray matter metabotropic glutamate receptors modulate formalin-induced nociception.

The role played by periaqueductal gray (PAG) matter metabotropic glutamate receptors (mGluRs) in the modulation of persistent noxious stimulation was investigated in mice. The formalin test was used as a model of persistent pain. Intra-PAG microinjections of (S)-3, 5-DHPG (25 and 50 nmol/mouse) and L-CCG-I (30 and 60 nmol/mouse), agonists of group I and group II mGluRs, respectively, decreased the nociceptive response (-92+/-6% and -89+/-8%, respectively) during the late phase. No change of the early nociceptive phase was observed after (S)-3,5-DHPG or L-CCG-I treatments. These effects were antagonized by a pretreatment with CPCCOEt (40 nmol/mouse) and (2S)-alpha-EGlu (30 nmol/mouse). CPCCOEt is a selective antagonist of group I mGlu receptors, while (2S)-alpha-EGlu is an antagonist of group II. Intra-PAG microinjections of L-SOP (60 and 120 nmol/mouse), a selective agonist of group III mGluRs, induced an increase of the nociceptive response (+95+/-7%) during the late hyperalgesic phase. (R,S)-alpha-M-SOP (70 nmol/mouse), a selective antagonist of group III mGluRs, completely antagonized the L-SOP-induced effect. These results show that PAG mGluRs participate in modulating the late hyperalgesic behaviours induced by formalin. It seems, therefore, possible that group I and group II mGluRs positively modulate PAG antinociceptive descending pathway following a persistent noxious stimulation, while group III mGluRs modulate it negatively.

Animals↗
PubMed2000

Effects of persistent nociception on periaqueductal gray glycine release.

Glycine is a candidate nociception inhibitory transmitter in specific brain regions, like for example the spinal cord, the thalamic nuclei and the periaqueductal gray matter. However, quantitative changes in glycine released in these brain regions during peripheral inflammation episodes have not been characterized in awake animals. To address this issue, an in vivo microdialysis study was carried out in freely moving rats in order to analyse periaqueductal gray matter extracellular glycine concentration following unilateral formalin injection into the dorsal skin of the right hind-paw. The extracellular concentration of glutamine was also evaluated in order to analyse whether or not a non-neurotransmitter amino acid was equally modified. Intra-periaqueductal gray matter tetrodotoxin perfusion reduced extracellular glycine concentration (-44+/-5%), but did not change the glutamine dialysate values. Peripheral injection of formalin reduced the glycine release during the early phase (-62+/-8%) and the late phase (-36+/-6%) of hyperalgesia, although not during the analgesic period. Perfusion with naloxone (300microM) neither prevented the formalin-induced decreases in extacellular glycine concentration, nor modified the perfusate basal values of glycine and glutamine. These results show that, contrary to what has been recognized on the interactive role of opioids and GABA into the periaqueductal gray matter (i.e. opioid disinhibition), endogenous opioids seem not to modulate the activity of glycinergic neurons in the same midbrain area. In the light of these preliminary data, it is reasonable to suppose that GABA and glycine are probably not co-released at the level of periaqueductal gray matter of the rat.

Animals↗
PubMed1999

Periaqueductal gray matter glutamate and GABA decrease following subcutaneous formalin injection in rat.

Glutamate and GABA are important nociception modulating transmitters in specific brain regions, i.e. the spinal cord, the thalamic nuclei and the periaqueductal gray (PAG). However, quantitative and topographical changes in glutamate and GABA release in these brain regions during peripheral inflammation episodes have not been characterized in awake animals. To address this issue, an in vivo microdialysis study was carried out in freely moving rats in order to analyze PAG extracellular glutamate and GABA concentrations following unilateral formalin injection into the dorsal skin of the right hind-paw. Both glutamate and GABA release decreased after the injection of formalin during phase I and phase II of hyperalgesia. Because naloxone prevented the decrease of GABA and glutamate release induced by formalin, this study shows that, in vivo, a nociceptive stimulation may activate opioidergic fibres into the PAG. The increased release of endogenous opioids may, in turn, inhibit the activity of the GABAergic neurons (i.e. opioid disinhibition). Formalin injection also decreased extracellular glutamate concentration. However, we found that intra-PAG perfusion with tetrodotoxin only decreased GABA, but not glutamate dialysate values. Although it should be reasonable to speculate that opioids also inhibit glutamate fibres, further investigation is needed to clarify whether or not the dialysate glutamate we measured reflects change in the metabolism or neurotransmitter pool of this amino acid.

Analysis of Variance↗
PubMed1998

Characterisation of mGluRs which modulate nociception in the PAG of the mouse.

The contribution of metabotropic glutamate receptors (mGluRs) to the modulation of nociception by the periaqueductal gray (PAG) matter was investigated in mice. Intra-PAG microinjection of (IS,3R)-ACPD, an agonist of groups I and II mGluRs, as well as (S)-3,5-DHPG, a selective agonist of group I mGluRs, increased the latency of the nociceptive reaction (NR) in the hot plate test. (RS)-AIDA, an antagonist of group I mGluRs, antagonized the effect of (S)-3,5-DHPG, but changed the effect induced by (1S,3R)-ACPD in that a decrease in the latency for the NR could now be observed. L-CCG-I and L-SOP, which are agonists of groups II and III mGluRs respectively, decreased the latency of the NR. (2S)-alpha-EGlu and (RS)-alpha-MSOP, which are antagonists of groups II and III mGluRs, respectively, antagonized the effect of L-CCG-I and L-SOP. (RS)-AIDA and (RS)-alpha-MSOP alone decreased and increased, respectively, the latency of the NR with the highest doses used. (2S)-alpha-EGlu alone did not change significantly the latency of the NR. Intra-PAG microinjection of LH, an agonist of ionotropic glutamate receptors, induced a dose-dependent analgesia which was blocked by pretreatment with DL-AP5, a selective antagonist of NMDA receptors. No mGluRs antagonists were able to prevent LH-induced analgesia. These results emphasize the possible involvement of mGluRs in the modulation of nociception. It seems that activation of group I mGluRs potentiates, while groups II and III mGluRs decrease, the activity of the PAG for the modulation of nociception.

2-Amino-5-phosphonovalerate↗
PubMed1998

The role of A3 adenosine receptors in central regulation of arterial blood pressure.

1. Pharmacological studies have suggested that A3 receptors are present on central neurons. Recently this adenosine receptor subtype has been identified in the rat and its presence in the central nervous system has been confirmed. 2. In this study we investigated the effects of acute intracerebroventricular (i.c.v.) injections of N6-2-(4-aminophenyl)-ethyladenosine (APNEA), a non-selective A3 adenosine receptor agonist, on arterial blood pressure (ABP) and heart rate (HR), after treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective antagonist of A1 adenosine receptors. 3. Anaesthetized rats, after DPCPX (12 microg(-1) kg i.c.v.), were treated with APNEA (0.4-4 microg kg(-1) i.c.v.) resulting in a transitory and dose-dependent decrease in arterial blood pressure without a change in heart rate. APNEA also induced hypotensive responses after i.c.v. pretreatment with aminophylline, at a dose of 20 microg kg(-1). In contrast, pretreatment 48 h before, with 4 microg kg(-1) i.c.v. of pertussis toxin reduced the hypotensive effect induced by APNEA. Administration of APNEA at a higher dose (20 microg kg(-1) i.c.v.), after DPCPX, induced a decrease in ABP of -66+/-5.4 mmHg and after 3 min a decrease in heart rate of -62+/-6.0 beats min(-1). Transection of the spinal cord abolished this significant fall in ABP, but not the decrease of HR. 4. These results suggest that a population of A3-receptors is present in the CNS, whose activation induces a decrease in blood pressure with no change of heart rate.

Animals↗
PubMed1997

Evidence for non-adrenergic non-cholinergic contractile responses in bovine and swine trachea.

Non-adrenergic non-cholinergic (NANC) contraction of airway smooth muscle has been observed in some but not all animal species. The aim of this study was to investigate the NANC-contractile responses in bovine and swine trachea. Proximal and distal bovine and swine trachea were cut in strips and placed in 10 ml organ baths equilibrated in Krebs Henseleit (KH) solution and electrically stimulated (10 sec, 60 V, 2 ms, 4, 10 and 30 Hz). Contractile frequency response curves performed in the presence of the muscarinic antagonist, atropine (100 mM), the angiotensin converting enzyme inhibitor, captopril (1 microM) and the neutral endopeptidase inhibitor, thiorphan (1 microM), added 30 min prior to electrical field stimulation (EFS). In some tissues, incubated with atropine thiorphan and captopril, were also evaluated the effects of a pretreatment with capsaicin (10 microM) or a selective NK1 receptor antagonist, SR 14033 (100 nM) added to the baths 30 min prior to EFS. Bovine and swine proximal and distal tracheal preparations contracted in a frequency-dependent manner to EFS (4, 10 and 30 Hz). Some experiments were also performed with substance P (0.1 nM to 1 microM) in absence or in presence of SR 14033 (10 nM or 100 nM). At the maximum frequency tested (30 Hz), the contractile response elicited in bovine proximal and distal preparations was 194.5 +/- 17.1% and 229.7 +/- 24.1%, of ACh (100 microM), respectively. Similarly, the contractile response elicited by EFS (30 Hz) in swine proximal and distal preparations was 187.2 +/- 12.1% and 181.6 +/- 9.2% of ACh (100 microM), respectively. In tissues incubated with atropine, a significant decrease in smooth muscle sensitivity to EFS was observed (P < 0.05). When tissues were pretreated with captopril and thiorphan, a significant increase in the contractile response to EFS (30 Hz) was observed in all tested tissue preparations (bovine, proximal 210.1 +/- 14.4%, distal 264.3 +/- 16.2%; swine, proximal 199.3 +/- 14.9%, distal 206.3 +/- 16.2%, P < 0.05). In the presence of atropine, captopril and thiorphan a significant increase in the contractile response was observed in bovine and swine distal preparations compared with tissues incubated with atropine only (P < 0.05). These effects were antagonized by a pretreatment with a selective NK1 receptor antagonist, SR 14033. A pretreatment with capsaicin statistically (P < 0.05) enhanced EFS-induced contraction in all tested preparations respect to tissues incubated with atropine, thiorphan and captopril. Substance P induced a concentration dependent contraction of bovine and swine isolated tracheal preparations which was antagonized by a pretreatment with a selective NK1 receptor antagonist, SR 14033. No significant difference in the contractile potency (EC50) nor in maximum response (Emax) was observed to exogenously administered substance P between proximal and distal tracheal preparations. These data suggest that NANC contractile responses are present in bovine and swine trachea and are more evident in distal airways.

Animals↗
PubMed1997

Nitric oxide regulatory role in sensitized guinea pig trachea.

Nitric oxide (NO) has been cited to play an important regulatory role in airway function. Moreover, the NO synthase expression in models of inflammation is documented. The aim of this study was to investigate, in vitro, the NO modulation of cholinergic responses in sham-sensitized and ovalbumin-sensitized guinea pig trachea by using L-arginine (L-ARG), a precursor of NO synthesis, and L-Ng-nitro-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase. Our results showed that NO's ability to modulate cholinergic responses in ovalbumin-sensitized guinea pig trachea is lost. Indeed L-ARG and L-NAME modify acetylcholine sensitivity in sham-sensitized guinea pig but not in ovalbumin-sensitized guinea pig.

Acetylcholine↗
PubMed1997

[Problems associated with the use and monitoring of cyclosporin. Experience at a Clinical Pharmacology Service].

BACKGROUND: A study on cyclosporine A (CyA) monitoring in the January 1992-December 1995 period is reported. The aim of this work was to give epidemiological data on the use of CyA, to verify the progressive increase of CyA determinations and to evaluate the use in other diseases as well as to compare the different technics of CyA assay in blood samples, to stress the timing of blood samples and to underline the CyA monitoring importance. METHODS: The CyA dosage was evaluated by fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC). RESULTS: The study showed that 70% of CyA determinations come from patients undergone to renal, bone marrow and liver transplantations; the remaining 30% was associated to other diseases (psoriasis, uveitis, diabetes, rheumatoid arthritis). CONCLUSIONS: The results obtained showed a progressive and constant increase of CyA determinations. Moreover, the use of drug was increased in autoimmune diseases. It is stressed that CyA monitoring in blood samples is essential to optimize the therapeutic efficacy of drug and minimizing its toxicity.

Autoimmune Diseases↗
PubMed1996

Synthesis and pharmacological activity of some N,N-disubstituted 1-amino-2-phenyl-3H,12H-naphtho[1,2-b]pyrano[2,3-d]pyran-3-ones.

The synthesis of some N,N-disubstituted 1-amino-2-phenyl-3H,12H-naphtho[1,2-b]pyrano[2,3-d]pyran-3-ones 4, by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-naphtho[1,2-b]pyran-4-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds 4 showed antiarrhythmic and analgesic activities.

Anti-Arrhythmia Agents↗
PubMed1995

Effects of RO 5-4864 and PK 11195 on guinea pig trachea.

Previous reports have suggested a role played by peripheral benzodiazepine receptors (PBZ) in the regulation of calcium. The aid of this investigation was to evaluate the effects of Ro 5-4864 (PBZ agonist) and PK11195 (PBZ antagonist) in guinea pig trachea and their possible role in the regulation of calcium. Ro 5-4864 and PK 11195 showed spasmolytic effects on the contraction curve induced by acetylcholine. Moreover, Ro 5-4864, PK 11195 and diltiazem (a Ca2+ -antagonistic drug) shifted to the right the contraction curves induced by acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), or by Bay K 8644. These results demonstrate that the benzodiazepines and their antagonists may exhibit Ca2+ -antagonistic activity. Ro 5-4864 and PK 11195 may exert this effect at a site that is a component of, or is associated with, voltage operated calcium channels (VOC).

Acetylcholine↗
PubMed1991

Teicoplanin does not modify the hypoglycemic effects of phenformin or glibenclamide, nor the anticoagulant action of warfarin. Experimental study.

Eventual pharmacological interactions induced by teicoplanin administration associated with oral hypoglycemic (phenformin and glibenclamide) and oral anticoagulant (warfarin) drugs have been experimentally evaluated. The administration of teicoplanin (3-15 mg/kg/die by endoperitoneal route) to the rat for 4 days did not significantly (P greater than 0.05) modify glycemia, prothrombin and partial thromboplastin times, the hypoglycemic effect of phenformin (2.5 mg/kg/die/4 days) or glibenclamide (0.5 mg/kg/die/4 days) nor the anticoagulant effect of warfarin (0.5 mg/kg/die/4 days). In conclusion, our results document that teicoplanin does not interfere with the activity of phenformin, glibenclamide or sodium warfarin.

Administration, Oral↗
PubMedDate not supplied

[Pharmacologic interactions between quinolones and oral hypoglycemic agents. An experimental study on rabbits].

The association between antibiotics and oral hypoglycemic agents can determine various pharmacological interactions. The aim of our work has been to verify experimentally the eventual pharmacological interactions that may occur when some quinolones (nalidixic acid, ofloxacin, pefloxacin and sparfloxacin) are administered in association with oral hypoglycemic drugs (phenphormine and glibenclamide). Our results showed that ofloxacin, pefloxacin and sparfloxacin only at high dosages (not used in the human clinic) can increase the phenphormine and glibenclamide hypoglycemic effect. The nalidixic acid, just at therapeutic doses, is able to increase the hypoglycemic effect of the drugs studied.

Animals↗