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V de Novellis

Publications and source records attributed to V de Novellis.

14 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↗
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

Metabotropic glutamate receptors modulate serotonin release in the rat periaqueductal gray matter.

The role of metabotropic (mGluRs) and N-methyl-D-aspartate (NMDA) glutamate receptors on 5-hydroxytryptamine (5-HT) release has been studied in rat periaqueductal gray (PAG) matter by using in vivo microdialysis. (1S,3R)-aminocyclopentane- 1,3-dicarboxylic acid [(IS,3R)-ACPD; 0.5 or 1 mM], a group I/group II mGluRs agonist, increased the dialysate 5-HT concentration. (2S)-alpha-ethylglutamic acid (EGlu; 1 mM), an antagonist of group II mGluRs, but not (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 mM), an antagonist of group I mGluRs, antagonized the 1S,3R-ACPD-induced effect. (S)-3,5-dihydroxyphenylglycine (DHPG; 0.5 and 1 mM), an agonist of group I mGluRs, did not modify dialysate 5-HT. (2S, 3S, 4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG-I; 0.5 and I mM), an agonist of group II mGluRs, increased extracellular 5-HT. This effect was antagonized by EGlu. Similarly, L-serine-O-phosphate (L-SOP; 1 and 10 mM), an agonist of group III mGluRs, increased extracellular 5-HT and this effect was antagonized by (RS)-(alpha-methylserine O-phosphate (M-SOP; 1 mM), an antagonist of group III mGluRs. Out of the several N-methylD-aspartate concentrations used (NMDA; 10, 50, 100, 500 and 1000 microM) only the 50 microM infusion significantly decreased dialysate 5-HT. The GABA(A) receptor agonist, bicuculline (30 microM), increased 5-HT release on its own and antagonized the decrease caused by the opiate antagonist, naloxone (2 mM), as well as the increases caused by CCG-I or L-SOP. These data show that stimulation of PAG's group II/group II mGluRs increases 5-HT release, while stimulation of NMDA glutamate receptors may decrease it. We speculate that glutamate does not modulate 5-HT release in the PAG directly, but via activation of tonically active GABAergic interneurons.

Animals↗
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↗
PubMed1996

Opposing effects on blood pressure following the activation of metabotropic and ionotropic glutamate receptors in raphe obscurus in the anaesthetized rat.

The microinjection of L-glutamate (1-6 nmol/rat) and N-methyl-D-aspartate (NMDA 1-10 nmol/rat), ionotropic glutamate receptor (iGluR) agonists, into the nucleus raphe obscurus caused a concentration -dependent increase of arterial blood pressure. In contrast, (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD, 14-42 nmol/rat), a metabotropic glutamate receptor (mGluRs) agonist, caused a concentration-dependent decrease in blood pressure. Pretreatment with D,L-2-amino-phosphono valeric acid (2-APV, 5 nmol/rat) a selective NMDA iGluR antagonist, and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b] cyclohepten-5,10-imine hydrogen maleate (MK801, 0.9 nmol/rat), a noncompetitive NMDA iGluR antagonist, blocked both the glutamate and NMDA pressor responses, while pretreatment with (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 0.05 nmol/rat), a mGluR1 antagonist, increased the glutamate-induced pressor effects and blocked the fall in blood pressure induced by t-ACPD. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.4 nmol/rat) a non-NMDA iGluR antagonist, did not affected the glutamate-induced hypertension. These observations indicate opposing roles for ionotropic and metabotropic receptors in the glutamate-induced blood pressure changes elicited from the nucleus raphe obscurus. Moreover, we suggest that the glutamate-induced hypertension may be due to the activation of NMDA ionotropic receptor subtypes and the metabotropic receptors may influence this activation through a reduction of excitability at level of synapses.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Antiarrhythmic effects of LR-A/113 a new calcium antagonistic drug.

LR-A/113 is a benzothiazepine drug similar to diltiazem with Ca(2+)-antagonist properties. Our previous studies showed that LR-A/113 determines anthypertensive effects comparable to diltiazem in normotensive and hypertensive rats. The aim of this study is to determine LR-A/113 effects respect to verapamil and diltiazem on CaCl2, aconitine and ouabain arrhythmias. Experiments were carried out on normotensive anesthetized rats and guinea pigs treated with CaCl2, aconitine and ouabaine and pretreated or not with verapamil, diltiazem or LR-A/113. Verapamil, diltiazem and LR-A/113, significantly delayed onset of arrhythmias and cardiac standstill induced by CaCl2 and aconitine. Moreover, pretreatments with verapamil, diltiazem or LR-A/113 reduced occurrence of arrhythmias in animals. In our models of arrhythmias LR-A/113 showed a significant antiarrhythmic effect of a magnitude almost similar to diltiazem but lower than for verapamil.

Aconitine↗
PubMed1995

Nitric oxide participates in the hypotensive effect induced by adenosine A2 subtype receptor stimulation.

In a previous study, we demonstrated that adenosine plays an important role in the central control of the cardiovascular system with involvement of adenosine A2 rather than A1 subtype receptors. In the present study, we investigated the putative relationship between nitric oxide (NO) and adenosine in the central and peripheral control of the cardiovascular system. Adult male normotensive anesthetized rats were treated with N6-cyclohexyladenosine (CHA), an A1-purinoceptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2-purinoceptor agonist intracerebroventricularly (i.c.v. 3rd ventricle; 0.05-0.1-0.5 microgram/rat) and by intravenous injection (0.5-1-5 microgram kg-1 i.v.). CPCA and CHA induced a significant and dose-dependent decrease in arterial blood pressure (BP). CHA effects were less marked than CPA. Rats were pretreated with xanthine amine congener (XAC), and A1 adenosine antagonist, with 3,7-dimethyl-1-propargylxanthine (DMPX), an A2 adenosine antagonist (both administered at doses of 0.05 microgram/rat i.c.v. or 0.5 microgram kg-1 i.v.) and with N omega-nitro-L-arginine methyl ester, an NO synthase inhibitor, (L-NAME, 90 microgram/rat i.c.v. and 0.3 mg kg-1 i.v.). The intracerebroventricular and intravenous pretreatment with DMPX or L-NAME inhibited CPCA-induced hypotension; the effect of L-NAME was weaker than that of DMPX. The L-NAME inhibitory effect was reversed both in the central nervous system (CNS) and at the peripheral level by pretreatment with L-arginine (L-Arg; 90 mg kg-1 i.v.), a precursor of NO synthesis. Pretreatment with XAC, but not with L-NAME, reduced the hypotensive effect of CHA. Moreover, intracerebroventricular pretreatment with L-Arg (174 micrograms/rat) increased the hypotensive effect of CPCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

Vasomotor reactivity and catecholamine, arginine vasopressin plasma levels during ageing and development in rats.

Vascular reactivity, heart rate responses to vasoconstrictor and/or vasodilatator agents and catecholamine and arginine vasopressin turnover were studied in normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SHR), normolipemic Brown Norway (BN) and spontaneously hyperlipemic Yoshida (YOS) anaesthetized rats at 2, 6 and 18 months of age. In this study, we investigated whether ageing and development could affect cardiovascular reactivity to vasoactive substances and catecholamine and arginine vasopressin turnover. No significant changes in the pressor responses to noradrenaline and to carotid sinus baroreceptor stimulation were observed nor were there significant alterations in reflex tachycardia and bradycardia. Arginine vasopressin plasma levels also did not change with ageing and development. On the other hand, the hypotensive responses to isoprenaline decreased in old rats, acetylcholine relaxation effect increased with ageing and development in some rat strains (BN and YOS) and catecholamine plasma levels increased with ageing and development. Our results indicate that during ageing and development, vascular responsiveness to vasoconstrictor and/or vasodilatator agents, as well as amine turnover, may increase, decrease or not change at all depending on the neurotransmission system studied, and on the experimental model and/or animal tested.

Acetylcholine↗
PubMed1994

Effects of the intracerebroventricular administration of ketamine on centrogenic arrhythmias in anesthetized rats.

In urethane anesthetized rats the icv (lateral cerebral ventricle) administration of ketamine, at the highest utilized doses, induced bradypnea and sinus bradycardia in spontaneously breathing rats. Moreover, it partially antagonized the arrhythmogenic activities of sodium glutamate and sodium aspartate, as well as desipramine and ouabain. From these results, we conclude that ketamine had an inhibitory effect on the centrogenic arrhythmias not only acting at the level of NMDA subtype receptor, but also at beta 1 adrenergic central receptors. Moreover at high doses, ketamine can also induce centrogenic arrhythmias in spontaneously breathing rats.

Anesthesia↗
PubMed1993

Cardiovascular effects of adenosine and its analogs in anaesthetized rats.

In order to define the purinergic receptors subtype involved in the control of cardiovascular activity, the effects of intracerebroventricular (icv 3rd ventricle) or intravenous (i.v.) injection of purinergic agonists and antagonists were evaluated on arterial blood pressure and heart rate of anaesthetized normotensive adult male rats. Adenosine (Ado) an A1 and A2 purinergic receptors agonist, N6-cyclohexyladenosine (CHA), an A1 receptor agonist and 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), an A2 purinergic receptor agonist, were administered in rats by icv (0.01-0.05-0.1 microgram) and i.v. (0.1-0.5-1 microgram/kg) injections. The animals treated with adenosine were either pretreated with an A1 (8-cyclopenthyl-1,3-dimethylxanthine, CPT) an A2 (3,7dimethyl-1-propargylxanthine, DMPX) or an A1-A2 (aminophylline, APH) purinergic receptor antagonist by icv (0.05 microgram) or i.v. (0.5 microgram/kg) injected or not at all pretreated. Ado, CPCA and CHA produced a dose-dependent decrease in arterial blood pressure and heart rate. The effects of CHA were less marked than those caused by Ado and CPCA. The icv and i.v. pretreatment with aminophylline, CPT and DMPX inhibited arterial hypotension and bradycardia induced by Ado, CHA and CPCA. The inhibitor effects of aminophylline and DMPX were stronger than those caused by CPT. These results showed that in the cerebral areas near the 3rd ventricle the purinergic system plays an important role in the control of cardiovascular function. The involvement of A2 purinergic receptors after administration of adenosine or its analogs on central and peripheral cardiovascular activity was also confirmed.

Adenosine↗
PubMed1992

Central arrhythmogenic effects of N-methyl-D-aspartate (NMDA) in anesthetized rats: influence of the denervation of the carotid-sinus baroreceptors on the susceptibility to arrhythmias.

The intracerebroventricular (i.c.v.) administration of NMDA into urethane anesthetized rats could induce centrogenic cardiac arrhythmias. There were some important differences between sodium glutamate- and NMDA-induced arrhythmias which rendered it difficult to accept the assumption that glutamate-induced arrhythmias were due to the stimulation of only NMDA receptors. Denervation of the carotid-sinus baroreceptor zones enhanced the central arrhythmogenic activity of both sodium glutamate and NMDA.

Anesthesia↗
PubMedDate not supplied

Endothelin-1 in periaqueductal gray area of mice induces analgesia via glutamatergic receptors.

The aim of the study was to examine whether endothelin-1 (ET-1) injected into dorsolateral periaqueductal gray (PAG) area of mice produces antinociception. ET-1, from 1 to 4 pmol/mouse, induced antinociceptive effect in a dose-dependent manner. This antinociceptive effect was prevented by NMDA receptor antagonists (2-APV and MK-801) injected in the same area (2-APV) or by intraperitoneal route (MK-801). CNQX, a non-NMDA receptor antagonist, did not inhibit the ET-1 effects. Prazosin, an alpha 1-adrenergic blocking agent, also prevented the ET-1 antinociceptive effect. We suggest that the activation of NMDA glutamatergic receptors in the PAG area may be a necessary step for ET-1 induced antinociception.

2-Amino-5-phosphonovalerate↗