Biomedical subjects

M Hamann

Publications and source records attributed to M Hamann.

At least 19 recordsLinked to original sources

PubMed2006

Kinetics of dendritic cell chimerism and T cell chimerism in allogeneic hematopoietic stem cell recipients.

Dendritic cells (DC) as potent antigen-presenting cells (APC) and T cells as effector cells play an essential role in the pathophysiology of both graft-versus-host (GvH) and graft-versus-leukemia (GvL) reactions after transplantation. Therefore, we determined the kinetics of DC and T-cell chimerism establishment after allogeneic hematopoietic cell transplantation (AHCT) in a group of 144 patients, using fluorescence-activated cell sorting (FACS) or magnetic cell sorting (MACS) followed by FISH or STR-PCR analysis for chimerism evaluation. In all, three cell lines investigated (CD3(+) T cells, CD11c(+) DC1 and CD123(+) DC2), we found a rapid and consistent establishment of complete donor chimerism (CDC) in over 70% of all patients during the first 6 weeks after AHCT. The rate of patients with CDC increased significantly over time within the first year after transplantation. A related donor (P=0.004) as well as an underlying lymphatic leukemia (P=0.03) were found to be significantly associated with development of MC in T cells. No significant correlation between DC or T cell chimerism and GvHD or relapse was detected. Our results thus demonstrate a fast and stable CDC in DC1, DC2 and T cells after AHCT that continuously increases over time in nearly all patients.

Adolescent↗

PubMed2006

[Modified sacrocolpopexy combined with a Burch procedure for recurrent stress urinary incontinence].

PURPOSE: Surgical procedures for the treatment of stress urinary incontinence (SUI) due to pelvic organ prolapse have specific relapse rates, especially with regard to long-term results. The aim of this study was to investigate the efficacy of a combined surgical technique: sacrocolpopexy combined with a Burch procedure - in particular as an option for previously operated patients. PATIENTS AND METHODS: From 9/2001 to 8/2004, 33 patients (mean age: 65 years) underwent a modified sacrocolpopexy combined with a Burch procedure. Thirty-six (93 %) patients had previous pelvic operations, nineteen (58 %) of them had failure of prior prolapse surgery. All women presented with urinary incontinence, cystocele and vault prolapse. SUI was classified grade II to III in 67 % (n = 22) cases. Grade II - III genital prolapse was associated in 88 % (n = 29) of the patients. They were screened by preoperative video-urodynamics. Surgery consisted of a Burch procedure and modified abdominal sacrocolpopexy. The mean follow-up was 18 months (range: 10 - 30 months). Follow-up investigations included a symptom score and an urogynaecological examination. A subgroup of ten patients had additional postoperative video-urodynamics. RESULTS: In all cases the operative procedure was performed successfully. During the follow-up 73 % (n = 24) of the patients were dry, another 18 % (n = 6) showed significant improvement. The number of diurnal/nocturnal micturitions decreased significantly from 9.4 to 6.9 (p < 0.005) and 2.2 to 1.1 (p < 0.005), respectively. The daily use of incontinence pads, as well as the amount of residual urine, decreased significantly from n = 5.1 to n = 1.1 (p < 0.005) and 60 mL to 6.0 mL (p < 0.005). Postoperative urodynamics showed that the bladder function remained unaffected by the procedure regarding de novo detrusor overactivity. CONCLUSION: After a mean follow-up of 18 months the modified sacrocolpopexy combined with a Burch procedure, as described above, is a promising technique for highly morbid and preoperated patients.

Aged↗

PubMed2006

Age-related changes in striatal nitric oxide synthase-immunoreactive interneurones in the dystonic dtsz mutant hamster.

The dt(sz) mutant hamster represents a model of paroxysmal dyskinesia in which dystonic episodes can be age-dependently induced by stress. GABAergic interneurones which co-express calcium binding proteins were found to be reduced in the striatum of the dt(sz) mutant. Other types of striatal interneurones have so far not been examined. In the present study, we therefore determined the density of nitric oxide synthase (NOS)-immunoreactive interneurones in the striatum of the dt(sz) mutant in comparison with nondystonic control hamsters. At the age of most marked expression of dystonia (30-40 days of life), the density of NOS-positive interneurones was decreased in the striatum of dt(sz) hamsters (-21%) in comparison with age-matched nondystonic control hamsters. Spontaneous remission of dystonia (age >90 days) coincided with a normalization of the density of NOS-reactive interneurones within the whole striatum of dt(sz) hamsters, but there remained a reduced density in distinct subregions. Together with previous findings the present data indicate that the development of striatal interneurones is retarded in mutant hamsters. The age-related deficit of NOS-reactive interneurones may at least in part contribute to an abnormal activity of striatal GABAergic projection neurones and thereby to the age-dependent dystonic syndrome in the dt(sz) mutant.

Age Factors↗

PubMed2005

[Prolapse surgery].

Operative cystocele/rectocele management and prolapse surgery have become increasingly important domains of urogynecologic surgery. The risk of prolapse surgery in women lies at around 11% today and one-third of these are reoperations. There are currently three competing operative procedures: (1) the transvaginal approach with a vaginae fixatio sacrospinalis vaginalis or sacrotuberalis, (2) transabdominal pelvic sacrocolpopexy, and (3) transabdominal laparoscopic sacrocolpopexy.We compared efficacy, reoperation rates, and complication rates in abdominal sacrocolpopexy to those found with the transvaginal or laparoscopic surgical approaches, by reviewing the literature of the last 10 years, including 1995, in an online search. Analysis of the accumulated data made it clear, moreover, that randomized, prospective studies on the three different operative procedures are missing; these are mandatory, however, to enable exact and objective assessment of efficacy, long-term results, and complication rates.

Colpotomy↗

PubMed2005

["Second line" polychemotherapy in metastatic urothelial cancer of the renal pelvis. Persisting partial remission by 18 treatment cycles of gemcitabine/paclitaxel after 24 treatment cycles gemcitabine/cisplatin "stable disease"].

Moderate activity of systemic chemotherapy for advanced urothelial cancer has been reported for more than 30 years. Only with the advent of potent combination therapy in the mid-1980s have clinically significant response rates and prolonged survival been documented. Due to the small number of cases and poor prognosis, knowledge is scant about the therapeutic effect of "second-line" polychemotherapy in metastatic upper tract urothelial cancer. We report an interesting case of a 59-year-old man suffering from urothelial cancer of the renal pelvis with pulmonary, lymphogenous, and bone metastases who had an unexpected response to "second-line" chemotherapy with only 2 treatment cycles of gemcitabine/paclitaxel (partial remission) after 24 treatment cycles of gemcitabine/cisplatin in "stable disease" with progression between the therapeutic intervals.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Spectrofluorimetric determination of manzamine A in spiked human urine and plasma.

The native fluorescence of manzamine A (a biologically active beta-carboline marine-derived alkaloid) has been studied under different conditions. The highest fluorescence intensity was obtained in methanol. Two wavelength settings were found to be suitable for excitation, 280 nm and 340 nm; while lambdamax emission was constant in both cases at 387 nm. The fluorescence intensity at 340/387 nm setting was 1.6 greater than that obtained at 280/387 nm settings. The calibration curves were rectilinear over the range 0.1-2.0 and 0.5-2.5 microg/ml for the two settings, respectively. The detection limits were 0.05 microg/ml (9.1 x 10(-9) M) and 0.1 microg/ml (1.82 x 10(-8) M) at 340/387 nm and 280/387 nm, respectively. The proposed method was applied to the determination of manzamine A in spiked human urine and plasma samples adopting the 340/387 nm wavelength setting, the % recoveries (n = 6) were 99.61 +/- 0.90 and 100.25 +/- 1.63, respectively.

Algorithms↗

PubMed2002

Patterns of lipid storage and mobilisation in the female green sea turtle ( Chelonia mydas).

Reproductive data from southern Queensland indicate that vitellogenesis in female Chelonia mydas takes approximately 8 months and is followed by a migration to a breeding area. At Heron Island, females lay multiple clutches over approximately 3 months. To investigate how females mobilise and store lipid during the breeding season we collected plasma, yolk, and fat tissue samples from females at a variety of stages during the nesting season. In breeding females, concentrations of plasma triglyceride increased seasonally. They reached peak concentrations during vitellogenesis and courtship, remained high throughout the nesting season, and then declined to a nadir after the last clutch. Plasma protein concentration increased throughout the breeding season, peaking following the last clutch for the season. Yolk lipids were highest during courtship and were similar throughout the nesting season, suggesting that uptake of lipid by ovarian follicles is completed prior to the beginning of the nesting season. Plasma triglyceride decreases in females with prolonged periods of unsuccessful nesting, and total lipid levels in adipose tissue and follicle yolks were significantly lower in atretic females. It appears that: (1) endogenous energy reserves can be reduced by stochastic environmental events (such as those reducing nesting success), and (2) a metabolic shift signalling the end of the nesting season is characterised by a drop in plasma triglycerides and slight increase in total plasma protein.

Adipose Tissue↗

PubMed2002

Changes in AMPA receptor binding in an animal model of inborn paroxysmal dystonia.

Previous pharmacological studies suggested that glutamatergic overactivity contributes to manifestation of dystonic attacks in mutant hamsters (dt(sz)), a model of idiopathic paroxysmal dystonia in which episodes of dystonia occur in response to stress. In the present study, [(3)H]AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor binding was determined by autoradiographic analyses in 41 brain (sub)regions of dt(sz) hamsters under basal conditions, i.e., in the absence of dystonia, and in a group of mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In comparison to nondystonic control hamsters the basal [(3)H]AMPA binding was significantly higher in the ventromedial and ventrolateral caudate putamen, the anterior cingulate cortex, the hippocampus, and the lateral septum of dystonic brains. During dystonic attacks the [(3)H]AMPA binding was significantly lower in the dorsomedial, dorsolateral, and posterior caudate putamen; the ventromedial thalamus; and the frontal cortex of mutant hamsters compared with control animals that were exposed to the same external stimulation. The basal increase in AMPA receptor density within limbic structures may contribute to the susceptibility of stress-inducible dystonic episodes in mutant hamsters. Since AMPA receptor activation is known to cause a fast reduction of the affinity and an internalization of postsynaptic AMPA receptors, the latter finding could reflect a glutamatergic overactivity within the striato-thalamo-cortical circuit during the expression of dystonia, which is in line with previous neurochemical and pharmacological data in dt(sz) hamsters.

Animals↗

PubMed2001

Metal levels in seston and marine fish flesh near industrial and metropolitan centres in South Australia.

Port Pirie is the site of the largest lead smelter in the world, depositing 250 t of zinc, and 100 t of lead annually into Spencer Gulf. Barker Inlet is adjacent to metropolitan Adelaide, and receives unknown quantities of urban and industrial discharges. Both areas are sites of major commercial and recreational fisheries, contained within delicately balanced marine wetland ecosystems, comprising large areas of mangrove and seagrass habitats. Aldrichetta forsteri and Sillago schomburgkii are major species within these fisheries and as estuarine-dependent species were chosen for this study as indicator species for the detection and monitoring of pollutant impacts in the nearshore marine ecosystems of South Australia. Seston sediment collectors were deployed at each site and analysed seasonally for the presence of cadmium, lead and copper. Flesh samples from A. forsteri and S. schomburgkii were examined seasonally for the presence of cadmium, lead and copper and the results correlated with levels found in the seston sediment at each site. Metal concentrations were also correlated with a biomarker of genotoxicity measured in the same animals (micronuclei in erythrocytes) that were reported previously. Seston levels of cadmium, lead and copper were highest at Port Pirie, followed by Barker Inlet and were lowest at Wills Creek, with cadmium undetectable at the latter site. Metals in seston varied considerably with season, with generally higher levels in winter samples. In fish flesh, metal levels followed broadly similar trends as for seston. Spearman rank correlations between metals in seston and in flesh were strongly positive. There was also a significant correlation between flesh concentrations of each metal and the frequency of micronuclei in erythrocytes. This study has shown that seston concentration of pollutant metals are high in areas of industrial activity, and that these levels are also reflected in metal content of fish flesh. Mean flesh levels of cadmium and copper did not exceed Australian health based maximum permitted levels of fish for human consumption, whereas flesh levels of lead in fish from Port Pirie and Barker Inlet exceeded these standards in each of the seasons monitored. This may represent a significant dietary source of lead in humans, especially at Port Pirie where human lead exposure from terrestrial sources is important. There may also be the potential for accumulation of metals in residents of metropolitan Adelaide whose diets are high in fish (and/or crustaceans), particularly estuarine-dependent species, such as A. forsteri and S. schomburgkii. The study also showed that a non-specific biomarker of genotoxicity (micronuclei in erythrocytes) is potentially useful as a monitoring technique in fish species to evaluate their exposure and genotoxic responses to pollutants in South Australian waters. These data represent a snapshot of the current situation in this area and may act as background levels against which future improvements or decrements in water quality may be compared.

Animals↗

PubMed2001

Effects of adenosine receptor agonists and antagonists in a genetic animal model of primary paroxysmal dystonia.

1. Recent studies have shown beneficial effects of an adenosine A(2A) receptor agonist in dt(sz) mutant hamsters, an animal model of paroxysmal dystonia, in which stress and consumption of coffee can precipitate dystonic attacks. This prompted us to examine the effects of adenosine receptor agonists and antagonists on severity of dystonia in dt(sz) hamsters in more detail. 2. The non-selective adenosine A(1)/A(2A) receptor antagonists, caffeine (10 - 20 mg kg(-1) i.p.) and theophylline (10 - 30 mg kg(-1) s.c.), worsened the dystonia in dt(sz) hamsters. 3. Aggravation of dystonia was also caused by the selective adenosine A(1)/A(2A) antagonist CGS 15943 (9-chloro2-2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine) at a dose of 30 mg kg(-1) i.p. and by the adenosine A(1) antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine; 20 - 30 mg kg(-1) i.p.), while the A(2) antagonist DMPX (3,7-dimethyl-1-propargylxanthine; 2 - 4 mg kg(-1) i.p.) and the highly selective A(2A) antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol; 2 - 5 mg kg(-1) i.p.) failed to exert any effects on dystonia. 4. In contrast to the antagonists, both the adenosine A(1) receptor agonist CPA (N(6)-cyclopentyladenosine; 0.1 - 1.0 mg kg(-1) i.p.) and the A(2A) agonist CGS 21680 (2p-(2carboxyethylphen-ethylamino-5'-N-ethylcarboxamindoadenosine; 0.1 - 2.0 mg kg(-1) i.p.) exerted a striking improvement of dystonia. 5. These data suggest that the precipitating effects of methylxanthines are, at least in part, related to their adenosine receptor antagonistic action. 6. Although adenosine receptor agonists can be regarded as interesting candidates for the therapy of paroxysmal dystonia, adverse effects may limit the therapeutic potential of adenosine A(1) agonists, while beneficial effects of the adenosine A(2A) agonist CGS 21680 were already found at well tolerated doses.

Adenosine↗

PubMed2001

Development of a sensitive assay to detect reversibly oxidized protein cysteine sulfhydryl groups.

Protein sulfhydryl groups can undergo reversible oxidation reactions in response to reactive oxygen and reactive nitrogen species. Sensitive detection of sulfhydryl group oxidation in specific proteins is required to further our understanding of protein redox changes in biological systems. In general, to detect reversible oxidation reactions the oxidized sulfur atom is reduced to a sulfhydryl group followed by a reaction with a quantifiable agent. Our aim was to develop a sensitive method to detect reversibly oxidized protein sulfhydryl groups in a Western blot format. Conjugation of methoxypolyethylene glycol-maleimide (MAL-PEG) to protein sulfhydryl groups was optimized. Once MAL-PEG forms a covalent bond with the protein, the MAL-PEG-protein conjugate can be detected as a band shift by western analysis. The efficiency of MAL-PEG conjugation to protein was determined with creatine kinase. MAL-PEG conjugated to approximately 100% of the available sulfhydryl groups on creatine kinase within 30 min. Band shift detection sensitivity was measured using the redox-regulated protein p53. MAL-PEG conjugation coupled to western analysis detected a minimum of 0.23 pmol of oxidized p53. The MAL-PEG conjugation method described in this communication can be used to assess the reversible sulfhydryl oxidation status of proteins for which antibodies suitable for western analysis are available.

Animals↗

PubMed2000

CGS 21680 exerts marked antidystonic effects in a genetic model of paroxysmal dyskinesia.

The effect of the adenosine A(2A) receptor agonist CGS 21680 (2-carboxyethyl)phenylethylamino]-5'-N-ethylcarbonyamido-ade nosine) on severity of dystonia was examined in genetically dystonic hamsters which exhibit attacks of dystonic and choreoathetotic disturbances in response to mild stress. CGS 21680 significantly reduced the severity of dystonia (0.5, 1.0 and 2.0 mg/kg i.p.). The marked antidystonic effects of CGS 21680 in the hamster model suggest that this compound may represent an interesting candidate for the therapy of paroxysmal dystonia. Furthermore, the present data indicate that the precipitating effect of caffeine in patients with paroxysmal dystonia is probably due to its adenosine receptor antagonistic action.

Adenosine↗

PubMed2000

Deficit of striatal parvalbumin-reactive GABAergic interneurons and decreased basal ganglia output in a genetic rodent model of idiopathic paroxysmal dystonia.

The underlying mechanisms of various types of hereditary dystonia, a common movement disorder, are still unknown. Recent findings in a genetic model of a type of paroxysmal dystonia, the dt(sz) mutant hamster, pointed to striatal dysfunctions. In the present study, immunhistochemical experiments demonstrated a marked decrease in the number and density of parvalbumin-immunoreactive GABAergic interneurons in all striatal subregions of mutant hamsters. To examine the functional relevance of the reduction of these inhibitory interneurons, the effects of the GABA(A) receptor agonist muscimol on severity of dystonia were examined after microinjections into the striatum and after systemic administrations. Muscimol improved the dystonic syndrome after striatal injections to a similar extent as after systemic treatment, supporting the importance of the deficiency of striatal GABAergic interneurons for the occurrence of the motor disturbances. The disinhibition of striatal GABAergic projection neurons, as suggested by recent extracellular single-unit recordings in dt(sz) hamsters, should lead to an abnormal neuronal activity in the basal ganglia output nuclei. Indeed, a significantly decreased basal discharge rate of entopeduncular neurons was found in dt(sz) hamsters. We conclude that a deficit of striatal GABAergic interneurons leads by disinhibition of striatal GABAergic projection neurons to a reduced activity in the entopeduncular nucleus, i.e., to a decreased basal ganglia output. This finding is in line with the current hypothesis about the pathophysiology of hyperkinesias. The results indicate that striatal interneurons deserve attention in basic and clinical research of those movement disorders.

Action Potentials↗

PubMed2000

Evidence for a hormonal tactic maximizing green turtle reproduction in response to a pervasive ecological stressor.

Mortality of breeding sea turtles due to excessive heat exposure after nesting activities is an unusual feature of the Raine Island green turtle rookery. Breeding turtles that fail to return to the ocean after oviposition can experience increasing body temperatures that exceed lethal limits (>39 degrees C) as ambient temperatures rise after sunrise. We investigated how acute increases in body temperature influenced plasma corticosterone (B) concentrations of individual turtles. Furthermore, interactions between progesterone (P) and testosterone (T) and increasing body temperature and the glucocorticoid corticosterone were examined for negative correlations. Breeding green turtles exhibited a 16-fold mean increase in plasma corticosterone concentration as body temperature (cloacal) rose from 28.2 to 40.7 degrees C in less than 6 h. However, the absolute increase in plasma B was small and much less than expected, despite the lethal stressor. Comparatively, the maximal B response to lethal heat stress was similar to plasma B concentrations obtained from breeding female turtles exposed to 8 h of capture stress. However, the maximal B response of breeding turtles exposed to heat and capture stressors was significantly less than the B response of nonbreeding adult female turtles subjected to an 8-h capture stressor. No negative correlations were observed between plasma T and plasma B, between plasma T and body temperature, between plasma P and plasma B, or between plasma P and body temperature. Our findings provide further evidence that reduced adrenocortical function operates in breeding green turtles in the presence of even the most pervasive of environmental stressors.

Adrenal Cortex↗

PubMed2000

Role of potassium channels in the control of renin secretion from isolated perfused rat kidneys.

This study aimed to assess the relevance of specific potassium channels, such as inwardly or outwardly rectifying and calcium-regulated potassium channels, to the control of renin secretion. For this purpose we examined the effects of the K+ channel blockers 4-aminopyridine (1 mmol/l), barium (100 micromol/l), tetraethylammonium (2 mmol/l) and apamin (200 nmol/l) on basal renin secretion, on renin secretion stimulated by isoproterenol (10 nmol/l) and on the inhibition of renin secretion by angiotensin II (100-300 pmol/l) in the isolated rat kidney perfused at constant pressure. Whilst all four K+ channel blockers increased renal vascular resistance, only 4-aminopyridine and barium attenuated isoproterenol-stimulated renin secretion in an additive fashion and augmented the inhibitory effect of angiotensin II. These effects of K+ channel blockers were not changed by the L-type calcium channel blocker amlodipine (5 pmol/l), indicating that their effects on renin secretion are not due to voltage-operated calcium influx. Our data, moreover, suggest that potassium efflux from renal juxtaglomerular cells is not important for the inhibitory action of angiotensin II on renin secretion. As a consequence it appears that the membrane potential of renal juxtaglomerular cells per se is relevant to renin secretion such that membrane depolarization inhibits the exocytosis of renin whilst hyperpolarization favors renin secretion. By their activity, potassium channels can contribute to membrane hyperpolarization and thus facilitate renin secretion.

4-Aminopyridine↗

PubMed2000

Mode of nitric oxide action on the renal vasculature.

Our study aimed to characterize the essential cellular pathways along which nitric oxide (NO) exerts its well-known vasodilatatory properties in the kidney. Using the isolated perfused rat kidney model we examined the roles of potassium channels, cGMP-protein kinase activity and cAMP-phosphodiesterases (PDE) in the effect of NO on renovascular resistance. We found that neither potassium channel activity nor G-kinase activity was essential for the vasodilatatory effect of NO. The effect of NO, however, was essentially mimicked by pharmacological inhibition of PDE-3, which is a cGMP-inhibitable PDE. As PDE-3 is strongly expressed in renal preglomerular vessels and NO stimulates cGMP formation in renal vessels, it appears likely that inhibition of cAMP degradation and consequently the cAMP pathway are crucially involved in mediating the effects of NO on renal vascular resistance.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1998

Stimulation of renin secretion by nitric oxide is mediated by phosphodiesterase 3.

This study aimed to characterize the cellular pathways along which nitric oxide (NO) stimulates renin secretion from the kidney. Using the isolated perfused rat kidney model we found that renin secretion stimulated 4- to 8-fold by low perfusion pressure (40 mmHg), by macula densa inhibition (100 micromol/liter of bumetanide), and by adenylate cyclase activation (3 nmol/liter of isoproterenol) was markedly attenuated by the NO synthase inhibitor nitro-L-arginine methyl ester (L-Name) (1 mM) and that the inhibition by L-Name was compensated by the NO-donor sodium nitroprusside (SNP) (10 micromol/liter). Similarly, inhibition of cAMP degradation by blockade of phosphodiesterase 1 (PDE-1) (20 micromol/liter of 8-methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine) or of PDE-4 (20 micromol/liter of rolipram) caused a 3- to 4-fold stimulation of renin secretion that was attenuated by L-Name and that was even overcompensated by sodium nitroprusside. Inhibition of PDE-3 by 20 micromol/liter of milrinone or by 200 nmol/liter of trequinsin caused a 5- to 6-fold stimulation of renin secretion that was slightly enhanced by NO synthase inhibition and moderately attenuated by NO donation. Because PDE-3 is a cGMP-inhibited cAMP-PDE the role of endogenous cGMP for the effects of NO was examined by the use of the specific guanylate cyclase inhibitor 1-H-(1,2,4)oxodiazolo(4,3a)quinoxalin-1-one (20 micromol). In the presence of 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1-one the effect of NO on renin secretion was abolished, whereas PDE-3 inhibitors exerted their normal effects. These findings suggest that PDE-3 plays a major role for the cAMP control of renin secretion. Our findings are compatible with the idea that the stimulatory effects of endogenous and exogenous NO on renin secretion are mediated by a cGMP-induced inhibition of cAMP degradation.

1-Methyl-3-isobutylxanthine↗

PubMed1998

Spillover-mediated transmission at inhibitory synapses promoted by high affinity alpha6 subunit GABA(A) receptors and glomerular geometry.

Divergence and convergence of synaptic connections make a crucial contribution to the information processing capacity of the brain. Until recently, it was thought that transmitter released at a synapse affected only a specific postsynaptic cell. We show here that spillover of inhibitory transmitter at the Golgi to granule cell synapse produces significant cross-talk to non-postsynaptic cells, which is promoted both by the anatomical specialization of this glomerular synapse and by the presence of the high affinity alpha6 subunit-containing GABA(A) receptor in granule cells. Cross-talk is manifested as a novel slow rising and decaying small amplitude inhibitory postsynaptic current (IPSC) that can also contribute a long-lasting component to more typical IPSCs, which is prolonged by inhibition of the neuronal GABA transporter GAT-1. Because of the long duration of IPSCs generated by spillover, the total charge carried is three times that of IPSCs generated by directly connected terminals. GABA spillover within the mossy fiber glomerulus may play an important role in regulating the number of granule cells active in the cerebellar cortex, a regulation that is suggested by theoretical models to optimize cerebellar information processing.

Animals↗