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Biomedical subjects

J de Vente

Publications and source records attributed to J de Vente.

At least 19 recordsLinked to original sources

The olive oil antioxidant hydroxytyrosol efficiently protects against the oxidative stress-induced impairment of the NObullet response of isolated rat aorta.

The Mediterranean diet, which is abundant in antioxidants, is associated with a relatively low incidence of coronary heart disease. Olive oil and olives, which contain the antioxidants hydroxytyrosol, oleuropein, and tyrosol, are important components of this diet. In this study, the effects of oxidative stress on the nitric oxide radical (NO(*))-mediated relaxation of rat aorta and the protection by these antioxidants were determined. Cumene hydroperoxide (CHP) was used to mimic oxidative stress induced by lipid hydroperoxides, which is mediated by the formation of hydroxyl radicals (OH(*)). CHP (300 microM) impaired the NO(*)-mediated relaxation of rat aorta by the acetylcholine receptor agonist carbachol (P < 0.05). This was due to a reduction in NO(*) production. A diminished NO(*)-mediated relaxation disturbs the vascular tone and leads to a rise in blood pressure, which is a well-established risk factor for coronary heart disease. Hydroxytyrosol (10 microM) efficiently protected the aorta against the CHP-induced impairment of the NO(*)-mediated relaxation (P < 0.05). Oleuropein, tyrosol, and homovanillic alcohol, a major metabolite of hydroxytyrosol, did not show protection. Moreover, hydroxytyrosol was found to be a potent OH(*) scavenger, which can be attributed to its catechol moiety. Because of its amphiphilic characteristics (octanol-water partitioning coefficient = 1.1), hydroxytyrosol will readily cross membranes and provide protection in the cytosol and membranes, including the water-lipid interface. The present study provides a molecular basis for the contribution of hydroxytyrosol to the benefits of the Mediterranean diet.

Animals↗

Selective blockade of phosphodiesterase types 2, 5 and 9 results in cyclic 3'5' guanosine monophosphate accumulation in retinal pigment epithelium cells.

AIM: To investigate which phosphodiesterase (PDE) is involved in regulating cyclic 3'5' guanosine monophosphate breakdown in retinal pigment epithelium (RPE) cells. METHODS: cGMP content in the cultured RPE cells (D407 cell line) was evaluated by immunocytochemistry in the presence of non-selective or isoform-selective PDE inhibitors in combination with the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). mRNA expression of PDE2, PDE5 and PDE9 was studied in cultured human RPE cells and rat RPE cell layers using non-radioactive in situ hybridisation. RESULTS: In the absence of PDE inhibitors, cGMP levels in cultured RPE cells are very low. cGMP accumulation was readily detected in cultured human RPE cells after incubation with Bay60-7550 as a selective PDE2 inhibitor, sildenafil as a selective PDE5 inhibitor or Sch51866 as a selective PDE9 inhibitor. In the presence of PDE inhibition, cGMP content increased markedly after stimulation of the particulate guanylyl cyclase. mRNA of PDE2,PDE5 and PDE9 was detected in all cultured human RPE cells and also in rat RPE cell layers. CONCLUSIONS: PDE2, PDE5 and PDE9 have a role in cGMP metabolism in RPE cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical spinal cord.

Natriuretic peptides (NP) and the corresponding receptors are present in the rodent spinal cord. We have studied the structures which respond to atrial natriuretic peptide, brain natriuretic peptide, or C-type natriuretic peptide with an increased synthesis of cGMP. NP-responsive cGMP-producing structures were observed in laminae I-III, and X, and in addition in ependymal cells, astrocytes and a subpopulation of dorsal root ganglion cells. As the cGMP concentration is controlled by the rate of synthesis and the rate of breakdown by phosphodiesterases, we studied NP-responsive structures in spinal cord slices incubated in the presence of different phosphodiesterase inhibitors. We studied EHNA and BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5 inhibitors, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. Double immunostainings showed that cGMP-IR colocalized partial with the vesicular acetylcholine transporter molecule in lamina X, with Substance P in a subpopulation of neuronal fibers situated dorsolateral, and with a subpopulation of CGRP-IR dorsal root ganglion neurons. Colocalization of cGMP-IR was absent with parvalbumin, synaptophysin, and the vesicular transporter molecules for GABA and glutamate. It is concluded that NPs in the spinal cord are probably involved in integrating intersegmental sensory processing in the spinal cord although the greater part of the NP-responsive cGMP-producing fibers could not be characterized. PDE2, 5, and 9 are involved in regulating NP-stimulated cGMP levels in the spinal cord. NPs may have a role in regulating cerebrospinal fluid homeostasis.

Animals↗

The role of phosphodiesterase isoforms 2, 5, and 9 in the regulation of NO-dependent and NO-independent cGMP production in the rat cervical spinal cord.

NO-responsive, cGMP-producing structures are abundantly present in the cervical spinal cord. NO-mediated cGMP synthesis has been implicated in nociceptive signaling and it has been demonstrated that cGMP has a role establishing synaptic connections in the spinal cord during development. As cGMP levels are controlled by the activity of soluble guanylyl cyclase (synthesis) and the phosphodiesterase (PDE) activity (breakdown), we studied the influence of PDE activity on NO-stimulated cGMP levels in the rat cervical spinal cord. cGMP-immunoreactivity (cGMP-IR) was localized in sections prepared from slices incubated in vitro. A number of reported PDE isoform-selective PDE inhibitors was studied in combination with diethylamineNONOate (DEANO) as a NO-donor including isobutyl-methylxanthine (IBMX) as a non-selective PDE inhibitor. We studied 8-methoxy-IBMX as a selective PDE1 inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5 inhibitor, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. cGMP-IR structures (nerve fibers, axons, and terminals) were characterized using the following neurochemical markers: vesicular transporter molecules for acetylcholine, GABA, and glutamate (type 1 and type 2), parvalbumin, glutamate transporter molecule EAAT3, synaptophysin, substance P, calcitonin gene-related peptide, and isolectin B4. Most intense cGMP-IR was observed in the dorsal lamina. Ventral motor neurons were devoid of cGMP-IR. cGMP-IR was observed in GABAergic, and glutamatergic terminals in all gray matter laminae. cGMP-IR was abundantly colocalized with anti-vesicular glutamate transporter 2 (vGLUT2), however not with the anti-vesicular glutamate transporter 1 (vGLUT1), suggesting a functional difference between structures expressing vGLUT1 or vGLUT2. cGMP-IR did not colocalize with substance P- or calcitonin-gene related peptide-IR structures, however did partially colocalize with isolectin B4 in the dorsal horn. cGMP-IR in cholinergic structures was observed in dorsal root fibers entering the spinal cord, occasionally in laminae 1-3, in laminae 8 and 9 in isolated boutons and in the C-type terminals, and in small cells and varicosities in lamina 10. This latter observation suggests that the proprioceptive interneurons arising in lamina 10 are also NO-responsive. No region-specific nor a constant co-expression of cGMP-IR with various neuronal markers was observed after incubation of the slices with one of the selected PDE inhibitors. Expression of the mRNA of PDE2, 5, and 9 was observed in all lamina. The ventral motor neurons and the ependymal cells lining the central canal expressed all three PDE isoforms. Incubation of the slices in the presence of IBMX, DEANO in combination with BAY 41-2272, a NO-independent activator of soluble guanylyl cyclase, provided evidence for endogenous NO synthesis in the slice preparations and enhanced cGMP-IR in all lamina. Under these conditions cGMP-IR colocalized with substance P in a subpopulation of substance P-IR fibers. It is concluded that NO functions as a retrograde neurotransmitter in the spinal cord but that also postsynaptic structures are NO-responsive by producing cGMP. cGMP-IR in a subpopulation of isolectin B4 positive fibers and boutons is indicative for a role of NO-cGMP signaling in nociceptive processing. cGMP levels in the spinal cord are controlled by the concerted action of a number of PDE isoforms, which can be present in the same cell.

3',5'-Cyclic-AMP Phosphodiesterases↗

Sensory collaterals, intramural ganglia and motor nerves in the guinea-pig bladder: evidence for intramural neural circuits.

The afferent output from the bladder is important for triggering micturition. This study identifies different types of afferent nerve and explores the connections of their collateral fibres on intramural ganglia and potential ganglionic targets. The experiments were performed on tissues from male guinea-pigs (n=16). Fibres positive for choline acetyl transferase (ChAT(+)) were found to originate close to the urothelium, to transit the sub-urothelial interstitial cell layer and to pass into the lamina propria. A different population of fibres, immunopositive for calcitonin gene-related peptide (CGRP), capsaicin receptors or neurofilament protein (NF), were seen to intertwine with the ChAT(+) fibres in the lamina propria. The ChAT(+) fibres did not express NF. Ganglia with ChAT(+) and NF(+) neurones were found in the lamina propria and muscle. ChAT(+) fibres, with pronounced terminal varicosities, were present on the nerve cell bodies. Two types were noted: NF(+) terminals and those with little or no NF (NF(-)) suggesting that their origins were the ChAT(+) afferent collaterals and the adjacent ganglia. Fibres containing CGRP or substance P were seen on the ganglionic cells. alpha1B adrenergic receptors were also found on the neurones indicative of adrenergic synapses. Thus, the ganglia had multiple inputs. Different types of ChAT(+) nerves were seen in the muscle: NF(+) and NF(-). The ChAT(+)/NF(+) nerves may represent a ganglionic output to the muscle. This complex neuronal network may therefore represent the elements generating and modulating bladder sensations. The role of such a scheme in bladder pathology and the therapeutic sites of action of anticholinergic and sympathomimetic drugs are discussed.

Animals↗

Nitric oxide-induced cGMP synthesis in the cholinergic system during the development and aging of the rat brain.

cGMP synthesis in cholinergic neurons of the basal forebrain, the caudate putamen, and the tegmento-pedunculopontine nucleus of the rat was studied during development after birth at P1, P4, P10, and P21, in the adult, and during aging. NO-mediated cGMP synthesis in these neurons was studied using the approach of in vitro incubation of brain slices in combination with cGMP-immunocytochemistry. The percentage of NO-responsive, cGMP-synthesizing cholinergic cells in the septum and diagonal band of Broca decreased from 75% to 6% in adult animals and to 2% in aged ones. In the caudate putamen, this decrease was from 81% to 21% in adult and 11% in aged animals. Cholinergic cells of the tegmento-pedunculopontine nucleus were unresponsive to NO and never showed cGMP-immunoreactivity. In addition, it was observed that the amount of NO-responsive, cGMP-synthesizing cholinergic fibers in the hippocampus declined in parallel with the maturation of the septal-hippocampal cholinergic pathway, whereas in the caudate putamen, this colocalization became complete 2 weeks after birth. It is concluded that the property of NO-mediated cGMP synthesis in the cholinergic nuclei of the forebrain is developmentally regulated after birth and that NO-cGMP signal transduction has a role in establishing cholinergic neuronal connections in the hippocampus and caudate putamen.

Age Factors↗

Expression of neuronal nitric oxide synthase (nNOS) and nitric-oxide-induced changes in cGMP in the urothelial layer of the guinea pig bladder.

The urothelium plays a sensory role responding to deformation of the bladder wall; this involves the release of adenosine trisphosphate (ATP) and nitric oxide (NO), which affect afferent nerve discharge and bladder sensation. The urothelial cells responsible for producing ATP and NO and the cellular targets, other than afferent nerves, for ATP and NO remain largely unexplored. Sub-urothelial interstitial cells (SU-ICs) lie immediately below the urothelium and respond to NO with a rise in cGMP. To determine which cells might target SU-ICs by producing NO, areas of dome, lateral wall and base wall were treated with isobutyl-methyl-xanthine, exposed to the NO donor diethylamino NONOate and then fixed for immunohistochemistry. Surface urothelial cells (SUCs) in the base and dome expressed neuronal nitric oxide synthase (nNOS), whereas those in the lateral wall did not. Distinct populations of SUCs were present in the bladder base. SUCs with significant amounts of nNOS lay adjacent to cells with low levels of nNOS. In specific base regions, the few SUCs present contained nNOS within discrete intracellular particles. In the basal urothelial cell (BUC) layer of the lateral wall, nNOS-positive (NOS(+)) BUCs neither showed an elevation in cGMP in response to NO, nor expressed the beta1 sub-unit of soluble guanylate cyclase, protein kinase I or protein kinase II. Thus, they produced but did not respond to NO. The BUC layer also stained for the stem cell factor c-Kit suggesting its involvement in urothelial cell development. No NOS(+) BUCs were present in the SUC-sparse region in the bladder base. Exogenous NO produced an elevation in cGMP in SUCs and SU-ICs. The distribution and proportion of these target cells varied between the dome, lateral wall and base. cGMP(+) SU-ICs were present as a dense layer in the bladder base but were rarely seen in the lateral wall, which contained nNOS(+) BUCs. No nNOS(+) BUCs and cGMP(+) SU-ICs were apparent in the dome. The degree of complexity in nNOS distribution and NO target cells is therefore greater than has previously been described and may reflect distinct physiological functions that have yet to be identified.

1-Methyl-3-isobutylxanthine↗

Dual effect of diazepam on cGMP levels in rat brain slices.

The effect of diazepam on NO-mediated cGMP synthesis was studied in rat brain slices. It was found that diazepam dose-dependently decreased cGMP synthesis in cerebellar slices, with an inhibition of 90% at 1 mM diazepam. cGMP levels in the presence of diazepam were not restored to control levels by the addition of 0.1 mM sodium nitroprusside, whereas the decrease in cerebellar cGMP levels induced by 0.1 mM L-NAME was restored by the simultaneous application of NO-donors. In addition to the decrease of cGMP levels in neuronal structures induced by 1 mM diazepam, we observed increased cGMP immunoreactivity in glial cells in the cerebellum, the hippocampus, and the cerebral cortex. The significance of this observation is discussed.

1-Methyl-3-isobutylxanthine↗

Inflammation markers in relation to cognition in a healthy aging population.

The relation between serum inflammatory protein levels and cognitive performance was investigated in a healthy population. Individuals were tested during 6 years of follow-up. Serum concentrations of 10 inflammatory proteins were correlated to cognitive speed (Letter-Digit Coding Test, LDCT), attention and information processing (Stroop) and memory (Word Learning). Haptoglobin levels at baseline correlated negatively with cognitive performance on the Stroop and Word Learning Recall test over the 6 years follow-up period. C-reactive protein (CRP) levels at baseline correlated negatively with performance on the Word Learning tests over the 6 years follow-up period. Thus, relatively high concentrations of haptoglobin and C-reactive protein may be indicative for impaired cognitive performance.

Adult↗

Combination of serum markers related to several mechanisms in Alzheimer's disease.

Alzheimer's disease (AD) probably involves several pathobiochemical mechanisms and this may be reflected by changes in different serum components. The present study investigated whether the combined analysis of serum molecules related to different mechanisms improves the discrimination of AD patients from healthy controls. Serum of patients with AD was analyzed for a broad spectrum of marker molecules, including 11 inflammatory proteins, 12 sterol intermediates and phytosterols, 2 brain-specific proteins and 4 constituents involved in homocysteine homeostasis. The serum molecule concentrations were combined in a logistic regression model, using a forward stepwise inclusion mode. The results showed that the combination of interleukin-6 (IL-6) receptor, protein alpha1 fraction, cysteine and cholesterol concentrations improved the discrimination between AD patients and healthy controls compared to the single markers. In conclusion, the results of this study have shown that the complex pathology in AD is reflected in a pattern of altered serum concentrations of several marker molecules related to several pathobiochemical mechanisms.

Adult↗

Decreased levels of cGMP in vitreous and subretinal fluid from eyes with retinal detachment.

BACKGROUND: Cyclic guanosine monophosphate (cGMP) is produced in different retinal cells, including photoreceptor cells, wherein cGMP mediates photo-transduction. CGMP is degraded by phosphodiesterases (PDE). The aim was to investigate whether retinal detachment alters intraocular cGMP levels in human eyes. METHODS: cGMP and PDE were determined in vitreous fluid from 50 eyes with a retinal detachment (group I) and in 20 control samples (group II) of vitreous fluid from eyes without retinal detachment. Group III consisted of subretinal fluid samples from 70 eyes with retinal detachment. RESULTS: cGMP in vitreous fluid from eyes with retinal detachment (6.5 (SD 1.7) nM) was decreased compared to controls (67.1 (10.0) nM) (p<0.0001). In subretinal fluid, the mean level of cGMP was 2.4 (0.2) nM. No PDE could be detected in any of the intraocular fluid samples of patients nor controls. A decrease in the mean level of cGMP in subretinal fluid of eyes with retinal detachment correlated with a longer duration of detachment (r = -0.45, p = 0.007). CONCLUSIONS: Retinal detachment was found to be associated with a decrease in vitreous cGMP concentration. In subretinal fluid, a low cGMP level correlated inversely with the duration of the detachment.

Adolescent↗

[Serum markers in relation to cognitive functioning in an aging population: results of the Maastricht Aging Study (MAAS)].

Little is known of the biochemical processes of cognitive decline during 'healthy' aging. Biological markers in body fluids, such as blood, could provide insight in those processes. In the present studies serum concentrations of different markers have been correlated to cognitive functioning of cognitively healthy aging individuals over a period of six years (mean age 57 years, SD 11, n = 93). Markers were related to mechanisms known to be involved in Alzheimer's disease, including inflammation, cholesterol homeostasis and homocysteine homeostasis. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test), and memory (Word Learning test: Total Words and Delayed Recall). Baseline concentrations of haptoglobine, homocysteine, lathosterol and lanosterol were negatively correlated with cognitive functioning on the Stroop test over the whole follow-up period of six years. Concentrations of all markers, i.e. haptoglobine, C-reactive protein, homocysteine, lathosterol and lanosterol, were also negatively correlated with functioning on the Word Learning test (Delayed Recall and for some markers also with the Total Words) over the whole six-years follow-up period. In conclusion, concentrations of serum markers related to inflammation, homocysteine and cholesterol homeostasis are not only associated with Alzheimer's disease, but also with cognitive functioning in the cognitively healthy aging population.

Adult↗

Homocysteine: a marker for cognitive performance? A longitudinal follow-up study.

The present prospective study investigated whether elevated total serum homocysteine concentration is a risk factor for cognitive decline. The outcomes were compared to the possible relation between cognition and vitamin B12 or folic acid. Cognitive performance of 144 normal aging individuals (aged 30-80 years) was tested at baseline and after six years of follow-up. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test) and verbal learning and memory (Word Learning Test Total; Delayed Recall). Serum concentrations of homocysteine, folic acid and vitamin B12 were determined. Serum concentrations of homocysteine correlated negatively with cognitive performance on the Word Learning tests at baseline, independent of age, sex, education level or folic acid concentration. Homocysteine concentration at baseline correlated negatively with cognitive performance on the Stroop and Word Learning tests during the whole six-year follow-up period. The folic acid concentration correlated to the Delayed Recall test at baseline only and no correlations were observed for vitamin B12. Thus, while a relation between vitamin B12 or folic acid and cognition was almost absent, elevated homocysteine concentrations were associated with prolonged lower cognitive performance in this normal aging population.

Adult↗

Baclofen inhibits ANP-mediated cyclic GMP synthesis in the rat cervical spinal cord.

The neurotransmitter gamma-aminobuteric acid (GABA) is believed to have a controlling action on spinal locomotor networks. In spasticity, spinal locomotor networks are thought to play a role. A well known drug in the treatment of spasticity is the GABA(B) agonist Baclofen. We report an inhibitory effect of Baclofen on the ANP-mediated cGMP synthesis in the superficial dorsal horn (laminae I-III) of the rat cervical spinal cord. This inhibitory effect of Baclofen could not be detected after incubation with the NO donor SNP. The clinical effect of Baclofen on the reduction of spasticity might be explained by an enhancement of GABAergic inhibition of ANP mediated cGMP concentration in the spinal cord dorsal horn, thus reducing afferent input.

Aging↗

Apoptosis in the rat spinal cord during postnatal development; the effect of perinatal asphyxia on programmed cell death.

The aim of our study was to investigate the effect of perinatal asphyxia on developmental apoptosis in the cervical and lumbar spinal cord in the neonatal rat. Perinatal asphyxia was induced by keeping pups at term in utero in a water bath at 37 degrees C for 20 min, followed by resuscitation. Effects of this treatment on developmental apoptosis were studied on postnatal days 2, 5 and 8 using terminal deoxynucleotidyl transferase (TdT)-dUTP-biotin nick end labelling (TUNEL) and caspase-3 staining. TUNEL positive cells were identified using double immunostaining. On postnatal day 2 an increase of 215% in TUNEL positive cells was detected (P=0.005) in laminae IV-VII of the lumbar spinal cord of rats which underwent perinatal asphyxia compared to controls. An increase of 55% compared to controls (P=0.03) was seen in laminae I-III of the lumbar spinal cord at postnatal day 8. TUNEL positive cells could be partly identified as microglia cells (ED1 positive) and oligodendrocytes (O4 positive). The effect of perinatal asphyxia on programmed cell death in the neonatal rat spinal cord was mainly observed in the intermediate zone and dorsal horn of the lumbar spinal cord. We conclude that perinatal asphyxia has a pronounced effect on the survival of cells in a specific region of the spinal cord and thus may have a profound effect on the development of motor networks.

Animals↗

Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat.

The present study investigated the effects of two cyclic GMP-specific phosphodiesterase enzyme type 5 inhibitors, sildenafil and vardenafil, on the memory performance in the object recognition task. Both compounds were given per orally (1, 3 and 10 mg/kg sildenafil; 0.1, 0.3, 1 and 3 mg/kg vardenafil) immediately after the exposure to two identical objects. The memory for the objects was tested 24 h later. Vehicle-treated rats spent equal times exploring a new and the familiar object demonstrating that they did not remember the familiar one. However, sildenafil improved the object discrimination performance of the rats with a high discrimination performance at a dose of 3 mg/kg. Rats treated with vardenafil also showed an improved object discrimination performance. Compared with sildenafil, vardenafil appeared to be even more potent in this respect since it already produced a high discrimination performance at a dose of 0.3 mg/kg. The effects of both compounds on cyclic GMP and cyclic AMP accumulation were studied in rat hippocampal slices incubated in vitro. Cyclic GMP levels were increased after incubation with the highest concentration of 100 microM vardenafil (together with 0.1 mM sodium nitroprusside), although no changes in cyclic GMP levels were detected after incubation with different concentrations of sildenafil. Both compounds had no effect on cyclic AMP levels. Additional cyclic GMP immunocytochemistry showed that incubation with vardenafil (in the presence of sodium nitroprusside) resulted in a concentration-dependent staining of cyclic GMP. Staining was predominantly found in neuronal fibres in the hippocampal CA2/CA3 region. It was already detected at a concentration of 0.1 microM vardenafil. Also positive fibres were detected after incubation with sildenafil but at a higher concentration of 10 microM. Taken together, these results suggest that inhibition of phosphodiesterase enzyme type 5 improves object recognition memory. This effect might be explained by increased levels of central cyclic GMP.

Animals↗

Distribution of cGMP in guinea pig autonomic ganglia after stimulation with sodium nitroprusside.

Nitric oxide (NO) is an intercellular messenger molecule in the nervous system and exerts its action in many regions by generating cyclic GMP (cGMP) via soluble guanylyl cyclase. In this study, on the male guinea pig, we have analyzed the localization of cGMP in some autonomic ganglia with immunohistochemistry after stimulation with sodium nitroprusside (SNP) as NO donor, and made correlations with the NO synthesizing enzyme NO synthase (NOS), tyrosine hydroxylase (TH) and some neuropeptides. The putative target neurons for NO were examined in the anterior pelvic ganglia (APGs), as well as some pre- and paravertebral sympathetic ganglia. The results show that cGMP-like immunoreactivity (LI) in the APG was in most cases observed in the TH-positive, NOS-negative neuron population after SNP stimulation, whereas the NOS-expressing cholinergic population mostly lacked detectable cGMP-LI. In the pre- and paravertebral ganglia, SNP stimulation increased cGMP levels to a much lesser extent than in the APGs. cGMP was also observed in blood vessels, in the ganglion capsule, and in some cases. possibly in satellite cells. We propose, as one alternative, that there is a functional, intraganglionic regulatory loop between the parasympathetic and sympathetic divisions of the APG, using the NO/cGMP pathway.

Animals↗

The three dimensional structure of the islands of Calleja: a single heterogenous cell complex.

The islands of Calleja in the rat brain stain brilliantly and stand out clearly using the NADPH-diaphorase histochemical staining. The 3-D structure of the Islands of Calleja was mapped in sagittal sections of young adult (3 months) and aged (28 months) animals. Contours were determined using a camera lucida method, and transferred to a computer equipped with an image analyzing system. Alignment of the sections using fixed anatomical anchers revealed that the islands of Calleja were one continuous structure at both ages studied. The structures varied between animals, and there was a pronounced left-right difference in the individual rats.

Animals↗