Search PubMed⌕ Search

Biomedical subjects

S Moncada

Publications and source records attributed to S Moncada.

At least 109 records · Page 6Linked to original sources
PubMed1995

The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha.

1. Myocardial dysfunction during septic shock is associated with enhanced production of cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). These cytokines depress cardiac mechanical function by a mechanism which is not well defined. 2. Bacterial endotoxin or cytokines cause the expression of Ca(2+)-independent nitric oxide (NO) synthase in cardiac myocytes, vascular endothelial cells and endocardial endothelial cells, causing enhanced production of NO. As NO has negative inotropic actions on cardiac muscle, we tested the sum effects of IL-1 beta plus TNF-alpha in the intact heart to determine whether enhanced expression of NO synthase activity in the cells that comprise the heart is involved in cardiac depression associated with cytokine stimulation. 3. Rat isolated working hearts perfused with IL-1 beta plus TNF-alpha showed a markedly greater depression in contractile function, measured as cardiac work, after 2 h of perfusion compared with time-matched control hearts. The depressant action of IL-1 beta plus TNF-alpha was first apparent after 1 h of perfusion; no early (15 min) cardiac depressant actions were seen. 4. The competitive inhibitor of Ca(2+)-dependent and Ca(2+)-independent NO synthases, NG-nitro-L-arginine methyl ester (L-NAME, 3 microM) when given concurrently with IL-1 beta plus TNF-alpha prevented the loss in contractile function such that these hearts after 2 h of perfusion had similar function to time-matched controls. L-NAME did not acutely reverse the loss of contractile function in hearts exposed for 2 h to IL-1 beta plus TNF-alpha. The protective action of L-NAME in the presence of cytokines was concentration-dependent and was not seen at a higher concentration (10 micro M) due to the significant reduction in coronary flow observed at this concentration.5. In contrast, when L-NAME (3 micro M) was given in the absence of IL-l beta plus TNF-alpha it depressed contractile function over the 2 h perfusion period by significantly reducing coronary flow.6. Inhibition of protein synthesis with cycloheximide (Cx) abolished the loss in function that occurred over 2h in both control and IL-1 beta plus TNF-a-treated hearts.7. Inducible, Ca2+-independent NO synthase activity was not observed in freshly isolated hearts but was observed in control hearts perfused for 2 h in vitro and was doubled in hearts perfused with IL-1 beta plus TNF-a. Cx prevented the expression of Ca2+-independent NO synthase in both control and cytokine-treated hearts.8. In summary, these results suggest that the depression of myocardial function by IL-l beta plus TNF-alpha is mediated, at least in part, by induction of Ca2+-independent NO synthase activity in the heart.

Amino Acid Oxidoreductases↗
PubMed1995

Characterization of nitrergic neurotransmission during short- and long-term electrical stimulation of the rabbit anococcygeus muscle.

1. Isolated preparations of rabbit anococcygeus muscle were exposed to electrical field stimulation (EFS; 50V, 0.3 ms duration, 0.08-40 Hz) for periods of 1-60 s (short-term EFS) or 10 min-2 h (long-term EFS). 2. Both short- and long-term EFS caused a contractile response which was enhanced by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (L-NOARG), showing that it is modulated by endogenous NO. 3. In preparations treated with scopolamine and guanethidine and in which a constrictor tone was induced by histamine, both short- and long-term EFS resulted in relaxation of the tissue. 4. Such relaxations were reversed by tetrodotoxin (TTX), omega-conotoxin, inhibitors of NO synthase and the NO scavenger, oxyhaemoglobin, indicating that they are neuronal in origin and nitrergic in nature. 5. The relaxations to long-term EFS persisted for the duration of the stimulation and were associated with sustained release of oxidation products of NO (NOx). The EFS-induced release of NOx was decreased by N-iminoethyl-L-ornithine (L-NIO), an inhibitor of NO synthase, and by TTX. 6. Inhibitors of NO synthase, in addition, increased the basal tone of the tissue and reduced the basal output of NOx. The basal output of NOx was also reduced by TTX. 7. Long-term EFS which induces approximately 50% of the maximum relaxation could be enhanced by addition of L-, but not D-, arginine to the perfusion medium. 8. These data show that there is a continuous basal release of NO from nitrergic nerve terminals which maintains a relaxant tone in the rabbit anococcygeus muscle. 9. In addition, NO is released during short- and long-term EFS which further relaxes the preparation and modulates sympathetic transmission. Activation of the L-argimne: NO pathway for periods up to2 h does not exhaust nitrergic transmission in any appreciable way.

Adenosine Triphosphate↗
PubMed1995

Induction of nitric oxide synthase and microvascular injury in the rat jejunum provoked by indomethacin.

1. The role of nitric oxide (NO) formed by the inducible isoform of NO synthase (NOS) in the generation of indomethacin-induced intestinal microvascular leakage was investigated in the rat. 2. Indomethacin (10 mg kg-1, s.c.) provoked an elevation of vascular leakage of radiolabelled human serum albumin in the jejunum over 48 h, commencing 18 h after its administration. This was associated with the induction of a calcium-independent NOS, as assessed by the conversion of radiolabelled L-arginine to citrulline. 3. Pretreatment with the glucocorticoid, dexamethasone (1 mg kg-1 day-1, s.c.) inhibited the induction of NOS and reduced jejunal microvascular leakage, determined 24 and 48 h after indomethacin. 4. Administration of the broad-spectrum antibiotic, ampicillin (800 mg kg-1 day-1, p.o.) likewise inhibited both the induction of NOS and the plasma leakage observed 24 and 48 h after indomethacin. 5. Ampicillin pretreatment did not, however, inhibit the induction of NOS, determined 5 h following endotoxin (3 mg kg-1 i.v.) challenge. Furthermore, incubation with ampicillin (1 mM, 10 min) did not inhibit the activity of the calcium-independent isoform in vitro. 6. Administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 2-10 mg kg-1, s.c.), at the time of the detectable expression of the inducible NOS (18 h after indomethacin), dose-dependently attenuated the plasma leakage, determined 6 later. This effect was reversed by pretreatment with L-arginine (300 mg kg-1, s.c.) 15 min before L-NAME. 7. These findings suggest that induction of a calcium-independent NOS following indomethacin administration involves gut bacteria and leads to microvascular injury in the rat jejunum.

Ampicillin↗
PubMed1995

Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat.

1. The effects of the nitric oxide (NO) donors, S-nitroso-glutathione (SNOG) and S-nitroso-N-acetyl-penicillamine (SNAP), on the acute intestinal microvascular dysfunction induced by NG-nitro-L-arginine methyl ester (L-NAME) in combination with low doses of endotoxin were investigated in the anaesthetized rat. 2. Administration of L-NAME (5 mg kg-1, s.c.) concurrently with E. coli lipopolysaccharide (LPS, 3 mg kg-1, i.v.) provoked the leakage of radiolabelled albumin in the ileum and colon, as a measure of microvascular damage, determined 1 h after challenge. 3. Intravenous infusion of SNOG or SNAP (1-10 micrograms kg-1 min-1) dose-dependently attenuated the microvascular leakage induced by L-NAME and LPS. 4. Infusion of the lowest doses of SNOG or SNAP (1 microgram kg-1 min-1, i.v.) that significantly reduced the albumin leakage, did not affect the increase in blood pressure in response to L-NAME in LPS-treated rats. Higher doses of SNOG or SNAP (5-10 micrograms kg-1 min-1, i.v.) dose-dependently reduced this increase in blood pressure. 5. In control studies, intravenous infusion of glutathione (10 micrograms kg-1 min-1) or N-acetyl-penicillamine (10 micrograms kg-1 min-1) had no effect on microvascular leakage in the ileum and colon induced by LPS and L-NAME. 6. Pretreatment with rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p., 4 h before challenge), which reduced the neutrophil count in peripheral arterial blood, also inhibited the microvascular leakage in the ileum and colon. 7. The protective effects of the nitrosothiol NO donors in this model may reflect, in part, modulation of neutrophil interactions within the microcirculation or actions on endothelial cell integrity, in addition to any local vasodilator action.

Animals↗
PubMed1995

The formation of nitric oxide donors from peroxynitrite.

1. Administration of peroxynitrite (ONOO-, 30-300 microM) caused relaxation of rabbit aortic strips superfused in series in a cascade. The compound responsible for this effect had a half-life greater than 20 s and could not therefore be either nitric oxide (NO) or ONOO- which have half-lives in the order of 1-2 s under these conditions. However the relaxation was inhibited by oxyhaemoglobin, suggesting the compound could be converted to NO in the vascular tissues or in the superfusate. 2. The products of the reactions between ONOO- and Krebs buffer containing 11 mM glucose, but not glucose-free Krebs buffer, caused relaxation of the bioassay tissues. These data suggest that stable NO donor(s) were formed from the reaction of ONOO- with glucose. We therefore prepared these NO donor(s) by the reaction of glucose solutions with ONOO- in order to characterize their ability to release NO. 3. These reaction product(s) caused relaxation in the cascade and inhibition of platelet aggregation. Both effects were dependent on the concentration of D-glucose, were equally effective if L-glucose was used as a reactant and were reversed by oxyhaemoglobin. 3. The products of the reaction between ONOO- and glucose or other biological molecules containing an alcohol functional group, such as fructose, glycerol, or glyceraldehyde, released NO in the presence of Cu2+and L-cysteine. 5. These results indicate that ONOO- reacts with sugars or other compounds containing an alcohol functional group(s) to form NO donors with the characteristics of organic nitrate/nitrites. This may represent a further detoxification pathway for ONOO- in vivo.

Animals↗
PubMed1995

Sequential induction of nitric oxide synthase by Corynebacterium parvum in different organs of the mouse.

1. The ability of Corynebacterium parvum (C. parvum) to induce nitric oxide (NO) synthase in the macrophage, spleen, liver, aorta, heart and brain, and to elevate plasma NO2-/NO3- in the mouse was investigated. In addition, the relationship between NO synthase activity and blood pressure was studied. 2. C. parvum (100 mg kg-1, i.p.) induced a time-dependent expression of a Ca(2+)-independent NO synthase in the macrophage, spleen, liver, aorta and heart. The time course of induction of the NO synthase varied such that the maximum enzyme activity was at day 8 in the macrophage and liver, day 12 in the spleen and heart and day 16 in the aorta. 3. There was no significant induction of a Ca(2+)-independent NO synthase in the brain, nor was there any change in the Ca(2+)-dependent enzyme in this organ, during the study period. 4. C. parvum produced a gradual decrease in blood pressure, with a maximum fall at day 16 (from 108 +/- 1 mmHg to 79 +/- 3 mmHg), which recovered gradually by day 28. 5. Plasma NO2-/NO3- was significantly elevated between days 8 and 24, with a maximum increase at day 12. 6. These results show that C. parvum induces a Ca(2+)-independent NO synthase in a number of tissues and that this induction occurs initially in macrophages and the liver. This suggests that induction of the NO synthase in the other tissues is secondary and probably the result of activation of macrophages and some cells of the liver. 7. Furthermore, the decrease in blood pressure induced by C. parvum is associated with the induction of NO synthase in the vasculature, whereas the increased concentration of plasma NO2-/NO3- seems to result from the generation of NO by a number of tissues.

Amino Acid Oxidoreductases↗
PubMed1995

Central vagal activation by an analogue of TRH stimulates gastric nitric oxide release in rats.

In the stomach nitric oxide (NO) appears to be involved in vagally induced cholinergic vasodilation and nonadrenergic, noncholinergic relaxation of the fundus. We investigated whether central vagal activation by intracisternal injection of a thyrotropin-releasing hormone (TRH) analogue stimulates gastric NO release in anesthetized rats. To quantitate gastric NO production, the luminal release of NO breakdown products, nitrite (NO2-) and nitrate (NO3-), were measured by the Griess method. Intracisternal injection of RX-77368 (30-300 ng) dose dependently stimulated gastric NO2- and NO3- release (P < 0.05) along with a significant acid secretory response (P < 0.05). The specific inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (10 mg/kg ip), completely blocked gastric luminal NO2- and NO3- release without affecting the acid secretory response to the highest dose of RX-77368. Either bilateral cervical vagotomy, hexamethonium (15 mg/kg ip), or atropine (1 mg/kg ip) abolished both gastric luminal release of NO-derived metabolites and the acid secretory responses to RX-77368. These results indicate that intracisternal injection of RX-77368 stimulates gastric release of NO through vagal nicotinic pathways and peripheral activation of muscarinic receptors. These findings provide evidence for central nervous system regulation of NO-mediated functions in the rat stomach through TRH-sensitive vagal pathways.

Amino Acid Oxidoreductases↗
PubMed1995

Megakaryocytes from patients with coronary atherosclerosis express the inducible nitric oxide synthase.

Endothelial and platelet generation of nitric oxide (NO) plays an important role in the regulation of hemostasis. Alterations in NO biosynthesis are described in atherosclerosis. We have investigated the NO pathway in megakaryocytes and platelets from patients with atherosclerosis and age-matched control subjects. Megakaryocytes and platelets were isolated from patients with severe coronary atherosclerosis (n = 19) and normal coronary arteries (n = 9) as demonstrated by selective angiography. Constitutive (Ca(2+)-dependent) and inducible (Ca(2+)-independent) NO synthase (cNOS and iNOS, respectively) activities were measured by using the citrulline assay and by immunostaining techniques using an anti-peptide antibody to iNOS. Megakaryocytes from patients with atherosclerosis expressed significantly greater amounts of iNOS (1.28 +/- 0.46 pmol citrulline.mg-1.min-1) than cNOS (0.29 +/- 0.40 pmol.mg-1.min-1). In contrast, megakaryocytes from patients with normal coronary arteries expressed significantly more cNOS (1.48 +/- 0.23 pmol.mg-1.min-1) than iNOS (0.49 +/- 0.40 pmol.mg-1.min-1). Platelets isolated from both groups showed no significant difference in cNOS expression, and no iNOS was seen in either group. Immunostaining confirmed the presence of the iNOS in megakaryocytes. These results suggest there is a link between the expression of iNOS in the megakaryocyte and atherosclerosis.

Amino Acid Oxidoreductases↗
PubMed1995

Nitric oxide synthesis in locust olfactory interneurones

The brain of the locust Schistocerca gregaria contains a nitric oxide synthase (NOS) that has similar properties to mammalian neuronal NOS. It catalyses the production of equimolar quantities of nitric oxide (NO) and citrulline from l-arginine in a Ca2+/calmodulin- and NADPH-dependent manner and is inhibited by the Nomega-nitro and Nomega-monomethyl analogues of l-arginine. In Western blots, an antiserum to the 160 kDa rat cerebellar NOS subunit recognises a locust brain protein with a molecular mass of approximately 135 kDa. NOS is located in several parts of the locust brain, including the mushroom bodies, but it is particularly abundant in the olfactory processing centres, the antennal lobes. Here it is present in two groups of local interneurones (a pair and a cluster of about 50) that project into the neuropile of the antennal lobes. The processes of these neurones terminate in numerous glomerulus-like structures where the synapses between primary olfactory receptor neurones and central interneurones are formed. NOS-containing local interneurones have also been identified in the mammalian olfactory bulb, suggesting that NO performs analogous functions in locust and mammalian olfactory systems. As yet, nothing is known about the role of NO in olfaction, but it seems likely that it is involved in the processing of chemosensory input to the brain. The locust antennal lobe may be an ideal 'simple' system in which this aspect of NO function can be examined.

Journal Article↗
PubMed1995

Molecular mechanisms and therapeutic strategies related to nitric oxide.

The formation of nitric oxide (NO) from L-arginine is now recognized as a ubiquitous biochemical pathway involved in the regulation of the cardiovascular, central, and peripheral nervous systems, as well as in other homeostatic mechanisms. The L-arginine:NO pathway comprises a substrate, L-arginine, a family of enzymes, the NO synthases, and at least one physiological effector system, the soluble guanylate cyclase. NO also inhibits enzymes in target cells and can interact with oxygen-derived radicals to produce other toxic substances. Thus, NO also plays a role in immunological host defense and in the pathophysiology of certain clinical conditions. Several steps in the L-arginine:NO pathway are amenable to manipulation. Some substances will change the concentration and/or actions of NO with consequences that, in certain cases, may be therapeutic. In addition, other agents themselves generate NO and thus mimic the actions of the endogenous mediator. This brief overview will discuss some possible interventions in the pathway and the potential benefits as well as undesirable side effects that might arise from them.

Animals↗
PubMed1995

Neuronal nitric oxide synthase immunoreactivity in the respiratory tract of the frog, Rana temporaria.

Physiological and histochemical studies have recently supported the notion that nitric oxide (NO) is the transduction signal responsible for the non-adrenergic, non-cholinergic relaxation of the vasculature as well as the airways of the mammalian lung. We report the presence of immunoreactivity to NO synthase (NOS) in nerve cell bodies and nerve fibres in the neural plexus of the buccal cavity and lungs of the frog, Rana temporaria, using the indirect immunocytochemical technique of avidin-biotin and the NADPH-diaphorase technique. The neural ganglia located next to the muscle layer and within the connective tissue of the buccal cavity were partially immunoreactive for NOS. In the lungs, NOS immunoreactivity occurred in nerve cell bodies, as well as in both myelinated and unmyelinated nerve fibres. Fine nerve fibres immunoreactive to NOS were observed within the muscle fibre bundles and next to the respiratory epithelium. Both the presence of NOS immunoreactivity and the positive histochemical reaction for NADPH-diaphorase in the neural plexus of amphibian respiratory tract suggests a broad evolutionary role for NO as a peripheral neurotransmitter.

Animals↗
PubMed1994

Localization of inducible nitric oxide synthase in acute renal allograft rejection in the rat.

There is increasing evidence for a role for nitric oxide (NO) in the alloimmune response and induction of NO synthesis occurs during allograft rejection. The aim of this study was to investigate the source of NO synthesis in rejecting allografts. Localization of inducible nitric oxide synthase (iNOS) was studied by immunohistochemistry, in a rat model of acute renal allograft rejection, in unmodified Lewis recipients in which rejection is complete 7 days after transplantation of F1 hybrid Lewis-Brown Norway kidneys. High levels of iNOS expression were found in infiltrating mononuclear cells in glomeruli and interstitium of rejecting kidneys; there was no expression in parenchymal renal cells, or in control isografts of either rat strain. Expression of iNOS in the cortex was present from 4 to 6 days posttransplantation, and had declined by the 7th day, where expression was principally in the medulla. The pattern of iNOS staining was similar to ED1 staining, a marker for rat macrophages. These findings suggest that infiltrating macrophages in the graft reaction are a prominent source of NO; this iNOS expression supports a role for NO in the modulation of local allogeneic responses, and possibly as a mediator of cytotoxic graft damage.

Amino Acid Oxidoreductases↗
PubMed1994

Peroxynitrite induces both vasodilatation and impaired vascular relaxation in the isolated perfused rat heart.

The effects of the oxidant species peroxynitrite (ONOO-) on coronary perfusion pressure and vasodilatation elicited by acetylcholine, isoproterenol, and S-nitroso-N-acetyl-DL-penicillamine were investigated in the isolated perfused rat heart. ONOO- (0.3-1000 microM) caused a concentration-dependent vasodilatation of the coronary vasculature. This dilator response was inhibited by oxyhemoglobin, indicating that it was due to the generation of nitric oxide. Tachyphylaxis to ONOO- developed rapidly, so that the response disappeared after three or four applications of this compound. ONOO- not only induced tachyphylaxis but also inhibited the vasodilatation induced by the three vasodilators studied. This latter effect of ONOO- was critically dependent on its concentration, since it occurred at 3 microM, which was subthreshold as a dilator, and at 1000 microM, which was supramaximal, but not at 30 and 100 microM. These latter concentrations inhibited the responses to vasodilators only in the presence of oxyhemoglobin. Thus, a wide range of concentrations of ONOO- induce a vascular dysfunction, as evidenced by the tachyphylaxis to its own vasodilator actions and the long-lasting impairment of the responses to other vasodilators. However, at the same time ONOO- generates nitric oxide, which at certain concentrations of ONOO- is sufficient to counteract its deleterious action. Coinfusion of S-nitroso-N-acetyl-DL-penicillamine or prostacyclin at low concentrations that did not produce vasodilatation also protected against ONOO(-)-induced vascular dysfunction: these compounds may be protective through a common mechanism, as yet undefined.

Acetylcholine↗
PubMed1994

Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty.

Platelet activation is associated with acute vessel occlusion and chronic restenosis after percutaneous transluminal coronary angioplasty (PTCA). Organic nitrates, which act by releasing the vasodilator and anti-platelet agent nitric oxide (NO), have a predominantly vasodilator action and cause hypotension at doses required to inhibit platelet activation. S-nitrosoglutathione (GSNO) is an NO donor with a preferential action on platelets. We investigated platelet activation in patients undergoing PTCA and the effect of GSNO. Blood was sampled from the coronary sinus to measure platelet surface expression of P-selectin and glycoprotein IIb/IIIa as indices of platelet activation. In 7 control patients, PTCA caused a rise in platelet surface expression of P-selectin and glycoprotein IIb/IIIa, which was maximal 5 minutes after PTCA, indicating increased platelet activation despite treatment with aspirin, glyceryl trinitrate, and heparin. 6 patients received an intracoronary infusion of GSNO, starting 10 min before PTCA. GSNO significantly inhibited the PTCA-induced increase in platelet surface expression of P-selectin and glycoprotein IIb/IIIa without altering blood pressure. These findings show that platelets are activated following PTCA and that GSNO can prevent this activation.

Aged↗
PubMed1994

Nitric oxide generation. A predictive parameter of acute allograft rejection.

The L-arginine:nitric oxide (NO) biosynthetic pathway has been proposed as an important mediator in host defense mechanisms and may therefore play a role in the acute allograft response. We have studied NO generation in liver allograft rejection and determined its value in immunological monitoring. Stable end products of this pathway have been determined serially in 50 primary liver recipients and compared with 2 known mediators and markers of acute allograft rejection (IL-2R positive lymphocytes and circulating TNF alpha). Plasma concentrations of acid-labile nitrosocompounds (NOx), which increased during acute allograft rejection (P < 0.0001), correlated with rejection severity and were reduced after administration of supplemental high dose glucocorticoids. Concentrations were significantly lower in nonrejection graft complications but were elevated during episodes of sepsis. Correlations between plasma NOx levels and circulating TNF-alpha (r = 0.451, P < 0.001) and IL-2R-positive lymphocytes in peripheral blood (r = 0.781, P < 0.001) were demonstrated. In a logistic analysis of these variables, plasma NOx was the most predictive parameter of an episode of acute cellular rejection. Nitric oxide generation in FK506-treated patients was lower compared with patients receiving a CsA-based immunosuppression regimen and was associated with a reduced frequency of acute rejection in the FK506 group. These data are consistent with a role for NO in the cellular alloantigen immune response and indicate that monitoring of plasma levels of NOx may be useful in the detection of acute allograft rejection.

Biomarkers↗
PubMed1994

Nitric oxide donors preferentially inhibit neuronally mediated rat gastric acid secretion.

Continuous i.v. infusion of the nitric oxide (NO) donors, S-nitroso-glutathione (10-50 micrograms kg-1 min-1) and S-nitroso-N-acetyl-penicillamine (10 micrograms kg-1 min-1) inhibited neuronally mediated gastric acid secretion, as induced by gastric distension (20 cm water) or i.v. bolus administration of 2-deoxy-D-glucose (150 mg kg-1) in the anaesthetized rat. By contrast, gastric acid responses to i.v. infusion of submaximal doses of pentagastrin (8 micrograms kg-1 h-1) or histamine (1 mg kg-1 h-1) were not influenced by these NO donors. These findings suggest that NO does not directly influence acid secretion in vivo but could play an inhibitory modulator role in neuronally mediated acid responses.

Animals↗
PubMed1994

Localization of nitric oxide synthase in the adult rat brain.

The distribution of the immunoreactivity to nitric oxide synthase has been examined from rostral to caudal areas of the rat central nervous system using light microscopy. Endogenous nitric oxide synthase was located using a specific polyclonal antiserum, produced against affinity purified nitric oxide synthase from whole rat brain, following the avidin-biotin peroxidase procedure. Immunoreactive cell bodies and processes showed a widespread distribution in the brain. In the telencephalon, immunoreactive structures were distributed in all areas of the cerebral cortex, the ventral endopiriform nucleus and claustrum, the main and accessory olfactory bulb, the anterior and posterior olfactory nuclei, the precommisural hippocampus, the taenia tecta, the nucleus accumbens, the stria terminalis, the caudate putamen, the olfactory tubercle and islands of Calleja, septum, globus pallidus and substantia innominata, hippocampus and amygdala. In the diencephalon, the immunoreactivity was largely found in both the hypothalamus and thalamus. In the hypothalamus, immunoreactive cell bodies were characteristically located in the perivascular-neurosecretory systems and mamillary bodies. In addition, immunoreactive nerve fibres were detected in the median eminence of the infundibular stem. The mesencephalon showed nitric oxide synthase immunoreactivity in the ventral tegmental area, the interpeduncular nucleus, the rostral linear nucleus of the raphe and the dorsal raphe nucleus. Immunoreactive structures were also found in the nuclei of the central grey, the peripeduncular nucleus and substantia nigra pars lateralis, the geniculate nucleus and in the superior and inferior colliculi. The pons displayed immunoreactive structures principally in the pedunculopontine and laterodorsal tegmental nuclei, the ventral tegmental nucleus, the reticulotegmental pontine nucleus, the parabrachial nucleus and locus coeruleus. In the medulla oblongata, immunoreactive neurons and processes were detected in the principal sensory trigeminal nucleus, the trapezoid body, the raphe magnus, the pontine reticular nuclei, the supragenual nucleus, the prepositus hypoglossal nucleus, the medial and spinal vestibular nuclei, the dorsal cochlear nucleus, the medullary reticular field, the nucleus of the solitary tract, the gracile and cuneate nuclei, the dorsal nucleus of the vagus nerve and the oral, interpolar and caudal parts of the spinal trigeminal nucleus. In the cerebellum, the stellate and basket cells showed immunoreactivity, which was also seen in the basket terminal fibres of the Purkinje cell layer. Isolated immunoreactive Purkinje cells were found in the vermis and parafloccular regions of the cerebellum. In the granular layer of the cerebellum, the granular cells and glomeruli were also immunoreactive. Numerous positive varicose nerve fibres and occasional neurons were also found in the lateral and interposed cerebellar nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Oxidoreductases↗