Search PubMed⌕ Search

Biomedical subjects

B Braun

Publications and source records attributed to B Braun.

At least 37 records · Page 2Linked to original sources
PubMed2001

Value of repeated multiplane transesophageal echocardiography in a patient with mitral valve ring abscess and left ventricular pseudoaneurysm.

Mitral valve ring abscess and ventricular pseudoaneurysm are rare complications of infective endocarditis. We describe the case of a 58-year-old man who was admitted to our hospital with sepsis caused by Staphylococcus aureus and in whom tricuspid and mitral valve endocarditis developed within 2 weeks. Despite widespread antibiotic therapy, the endocarditis proceeded to form a mitral valve ring abscess and a left ventricular pseudoaneurysm. The diagnosis was set by repeated multiplane transesophageal echocardiography and confirmed by heart surgery.

Abscess↗
PubMed2001

Upregulation of iNOS expression and phosphorylation of eIF-2alpha are paralleled by suppression of protein synthesis in rat hypothalamus in a closed head trauma model.

When the inducible form of nitric oxide synthase (iNOS) is expressed after challenge to the nervous system, it results in abnormally high concentrations of nitric oxide (NO). Under such conditions, NO could phosphorylate the eukaryotic translation initiation factor (eIF)-2alpha, thus suppressing protein synthesis in neurons that play a role in endocrine and autonomic functions. Using the Marmarou model of traumatic brain injury (TBI), we observed a rapid increase (at 4 h after TBI) of iNOS mRNA in magno- and parvocellular supraoptic and paraventricular neurons, declining gradually by approximately 30% at 24 h and by approximately 80% at 48 h. Western analysis indicated a trend towards increased iNOS protein synthesis at 4 h, which peaked at 8 h, and tended to decrease at the later time points. At the same time points, we detected immunocytochemically the phosphorylated form of eIF-2alpha (eIF-2alpha[P]) as cytoplasmic and more often as nuclear labeling. The incidence of double-labeled [iNOS and eIF-2alpha(P)] neuronal profiles, particularly at 24 h and 48 h after TBI, was high. De novo protein synthesis assessed quantitatively after infusion of 35S methionine/cysteine was reduced by approximately 20% at 4 h, remained depressed at 24 h, and did not return to control levels up to 48 h following the trauma. The results suggest that iNOS may trigger phosphorylation of eIF-2alpha, which in turn interferes with protein synthesis at the translational (ribosomal complex) and transcriptional (chromatin) levels. The depression in protein synthesis may include downregulation of iNOS itself, which could be an autoregulatory inhibitory feedback mechanism for NO synthesis. Excessive amounts of NO may also participate in dysfunction of hypothalamic circuits that underlie endocrine and autonomic alterations following TBI.

Animals↗
PubMed2001

Endocrine regulation of exercise substrate utilization in women compared to men.

During low to moderate intensity exercise, women utilize proportionally more lipid and less carbohydrate compared to men. Estrogen and progesterone may have direct effects on these differences by increasing lipolysis and/or constraining glucose production and utilization. Furthermore, sex steroids may have indirect effects through interactions with other hormones, especially catecholamines.

Adipose Tissue↗
PubMed2001

Women at altitude: forearm hemodynamics during acclimatization to 4,300 m with alpha(1)-adrenergic blockade.

We hypothesized that blockade of alpha(1)-adrenergic receptors would prevent the rise in peripheral vascular resistance that normally occurs during acclimatization. Sixteen eumenorrheic women were studied at sea level (SL) and at 4,300 m (days 3 and 10). Volunteers were randomly assigned to take the selective alpha(1)-blocker prazosin or placebo. Venous compliance, forearm vascular resistance, and blood flow were measured using plethysmography. Venous compliance fell by day 3 in all subjects (1.39 +/- 0.30 vs. 1.62 +/- 0.43 ml. Delta 30 mmHg(-1) x 100 ml tissue(-1) x min(-1) at SL, means +/- SD). Altitude interacted with prazosin treatment (P < 0.0001) such that compliance returned to SL values by day 10 in the prazosin-treated group (1.68 +/- 0.19) but not in the placebo-treated group (1.20 +/- 0.10, P < 0.05). By day 3 at 4,300 m, all women had significant falls in resistance (35.2 +/- 13.2 vs. 54.5 +/- 16.1 mmHg x ml(-1) x min(-1) at SL) and rises in blood flow (2.5 +/- 1.0 vs. 1.6 +/- 0.5 ml. 100 ml tissue(-1) x min(-1) at SL). By day 10, resistance and flow returned toward SL, but this return was less in the prazosin-treated group (resistance: 39.8 +/- 4.6 mmHg x ml(-1) x min(-1) with prazosin vs. 58.5 +/- 9.8 mmHg x ml(-1) x min(-1) with placebo; flow: 1.9 +/- 0.7 ml. 100 ml tissue(-1) x min(-1) with prazosin vs. 2.3 +/- 0.3 ml x 100 ml tissue(-1) x min(-1) with placebo, P < 0.05). Lower resistance related to higher circulating epinephrine in both groups (r = -0.50, P < 0.0001). Higher circulating norepinephrine related to lower venous compliance in the placebo-treated group (r = -0.42, P < 0.05). We conclude that alpha(1)-adrenergic stimulation modulates peripheral vascular changes during acclimatization.

Acclimatization↗
PubMed2001

Catecholamine responses to alpha-adrenergic blockade during exercise in women acutely exposed to altitude.

We have previously documented the importance of the sympathetic nervous system in acclimatizing to high altitude in men. The purpose of this investigation was to determine the extent to which alpha-adrenergic blockade affects the sympathoadrenal responses to exercise during acute high-altitude exposure in women. Twelve eumenorrheic women (24.7 +/- 1.3 yr, 70.6 +/- 2.6 kg) were studied at sea level and on day 2 of high-altitude exposure (4,300-m hypobaric chamber) in either their follicular or luteal phase. Subjects performed two graded-exercise tests at sea level (on separate days) on a bicycle ergometer after 3 days of taking either a placebo or an alpha-blocker (3 mg/day prazosin). Subjects also performed two similar exercise tests while at altitude. Effectiveness of blockade was determined by phenylephrine challenge. At sea level, plasma norepinephrine levels during exercise were 48% greater when subjects were alpha-blocked compared with their placebo trial. This difference was only 25% when subjects were studied at altitude. Plasma norepinephrine values were significantly elevated at altitude compared with sea level but to a greater extent for the placebo ( upward arrow 59%) vs. blocked ( upward arrow 35%) trial. A more dramatic effect of both altitude ( upward arrow 104% placebo vs. 95% blocked) and blockade ( upward arrow 50% sea level vs. 44% altitude) was observed for plasma epinephrine levels during exercise. No phase differences were observed across any condition studied. It was concluded that alpha-adrenergic blockade 1) resulted in a compensatory sympathoadrenal response during exercise at sea level and altitude, and 2) this effect was more pronounced for plasma epinephrine.

Adrenergic alpha-Agonists↗
PubMed2001

Gender alters impact of hypobaric hypoxia on adductor pollicis muscle performance.

Recently, we reported that, at similar voluntary force development during static submaximal intermittent contractions of the adductor pollicis muscle, fatigue developed more slowly in women than in men under conditions of normobaric normoxia (NN) (Acta Physiol Scand 167: 233-239, 1999). We postulated that the slower fatigue of women was due, in part, to a greater capacity for muscle oxidative phosphorylation. The present study examined whether a gender difference in adductor pollicis muscle performance also exists during acute exposure to hypobaric hypoxia (HH; 4,300-m altitude). Healthy young men (n = 12) and women (n = 21) performed repeated static contractions at 50% of maximal voluntary contraction (MVC) force of rested muscle for 5 s followed by 5 s of rest until exhaustion. MVC force was measured before and at the end of each minute of exercise and at exhaustion. Exhaustion was defined as an MVC force decline to 50% of that of rested muscle. For each gender, MVC force of rested muscle in HH was not significantly different from that in NN. MVC force tended to decline at a faster rate in HH than in NN for men but not for women. In both environments, MVC force declined faster (P < 0.01) for men than for women. For men, endurance time to exhaustion was shorter (P < 0.01) in HH than in NN [6.08 +/- 0.7 vs. 8.00 +/- 0.7 (SE) min]. However, for women, endurance time to exhaustion was similar (not significant) in HH (12.86 +/- 1.2 min) and NN (13.95 +/- 1.0 min). In both environments, endurance time to exhaustion was longer for women than for men (P < 0.01). Gender differences in the impact of HH on adductor pollicis muscle endurance persisted in a smaller number of men and women matched (n = 4 pairs) for MVC force of rested muscle and thus on submaximal absolute force and, by inference, ATP demand in both environments. In contrast to gender differences in the impact of HH on small-muscle (adductor pollicis) exercise performance, peak O(2) uptake during large-muscle exercise was lower in HH than in NN by a similar (P > 0.05) percentage for men and women (-27.6 +/- 2 and -25.1 +/- 2%, respectively). Our findings are consistent with the postulate of a higher adductor pollicis muscle oxidative capacity in women than in men and imply that isolated performance of muscle with a higher oxidative capacity may be less impaired when the muscle is exposed to HH.

Adult↗
PubMed2001

Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic blockade reduces insulin sensitivity.

After short-term exposure to high altitude (HA), men appear to be less sensitive to insulin than at sea level (SL). We hypothesized that the same would be true in women, that reduced insulin sensitivity would be directly related to the rise in plasma epinephrine concentrations at altitude, and that the addition of alpha-adrenergic blockade would potentiate the reduction. To test the hypotheses, 12 women consumed a high-carbohydrate meal at SL and after 16 h at simulated 4,300-m elevation (HA). Subjects were studied twice at each elevation: once with prazosin (Prz), an alpha(1)-adrenergic antagonist, and once with placebo (Pla). Mathematical models were used to assess insulin resistance based on fasting [homeostasis model assessment of insulin resistance (HOMA-IR)] and postprandial [composite model insulin sensitivity index (C-ISI)] glucose and insulin concentrations. Relative to SL-Pla (HOMA-IR: 1.86 +/- 0.35), insulin resistance was greater in HA-Pla (3.00 +/- 0.45; P < 0.05), SL-Prz (3.46 +/- 0.51; P < 0.01), and HA-Prz (2.82 +/- 0.43; P < 0.05). Insulin sensitivity was reduced in HA-Pla (C-ISI: 4.41 +/- 1.03; P < 0.01), SL-Prz (5.73 +/- 1.01; P < 0.05), and HA-Prz (4.18 +/- 0.99; P < 0.01) relative to SL-Pla (8.02 +/- 0.92). Plasma epinephrine was significantly elevated in HA-Pla (0.57 +/- 0.08 ng/ml; P < 0.01), SL-Prz (0.42 +/- 0.07; P < 0.05), and HA-Prz (0.82 +/- 0.07; P < 0.01) relative to SL-Pla (0.28 +/- 0.04), but correlations with HOMA-IR, HOMA-beta-cell function, and C-ISI were weak. In women, short-term exposure to simulated HA reduced insulin sensitivity compared with SL. The change does not appear to be directly mediated by a concurrent rise in plasma epinephrine concentrations.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

Women at altitude: ventilatory acclimatization at 4,300 m.

Women living at low altitudes or acclimatized to high altitudes have greater effective ventilation in the luteal (L) compared with follicular (F) menstrual cycle phase and compared with men. We hypothesized that ventilatory acclimatization to high altitude would occur more quickly and to a greater degree in 1) women in their L compared with women in their F menstrual cycle phase, and 2) in women compared with men. Studies were conducted on 22 eumenorrheic, unacclimatized, sea-level (SL) residents. Indexes of ventilatory acclimatization [resting ventilatory parameters, hypoxic ventilatory response, hypercapnic ventilatory response (HCVR)] were measured in 14 women in the F phase and in 8 other women in the L phase of their menstrual cycle, both at SL and again during a 12-day residence at 4,300 m. At SL only, ventilatory studies were also completed in both menstrual cycle phases in 12 subjects (i.e., within-subject comparison). In these subjects, SL alveolar ventilation (expressed as end-tidal PCO(2)) was greater in the L vs. F phase. Yet the comparison between L- and F-phase groups found similar levels of resting end-tidal PCO(2), hypoxic ventilatory response parameter A, HCVR slope, and HCVR parameter B, both at SL and 4,300 m. Moreover, these indexes of ventilatory acclimatization were not significantly different from those previously measured in men. Thus female lowlanders rapidly ascending to 4,300 m in either the L or F menstrual cycle phase have similar levels of alveolar ventilation and a time course for ventilatory acclimatization that is nearly identical to that reported in male lowlanders.

Acclimatization↗
PubMed2001

Erythropoiesis in women during 11 days at 4,300 m is not affected by menstrual cycle phase.

Because the ovarian steroid hormones, progesterone and estrogen, have higher blood levels in the luteal (L) than in the follicular (F) phase of the menstrual cycle, and because of their known effects on ventilation and hematopoiesis, we hypothesized that less hypoxemia and less erythropoiesis would occur in the L than the F phase of the cycle after arrival at altitude. We examined erythropoiesis with menstrual cycle phase in 16 women (age 22.6 +/- 0.6 yr). At sea level, 11 of 16 women were studied during both menstrual cycle phases, and, where comparison within women was available, cycle phase did not alter erythropoietin (n = 5), reticulocyte count (n = 10), and red cell volume (n = 9). When all 16 women were taken for 11 days to 4,300-m altitude (barometric pressure = 462 mmHg), paired comparisons within women showed no differences in ovarian hormone concentrations at sea level vs. altitude on menstrual cycle day 3 or 10 for either the F (n = 11) or the L (n = 5) phase groups. Arterial oxygen saturation did not differ between the F and L groups at altitude. There were no differences by cycle phase on day 11 at 4,300 m for erythropoietin [22.9 +/- 4.7 (L) vs. 18.8 +/- 3.4 mU/ml (F)], percent reticulocytes [1.9 +/- 0.1 (L) vs. 2.1 +/- 0.3% (F)], hemoglobin [13.5 +/- 0.3 (L) vs. 13.7 +/- 0.3 g/100 ml (F)], percent hematocrit [40.6 +/- 1.4 (L) vs. 40.7 +/- 1.0% (F)], red cell volume [31.1 +/- 3.6 (L) vs. 33.0 +/- 1.6 ml/kg (F)], and blood ferritin [8.9 +/- 1.7 (L) vs. 10.2 +/- 0.9 microg/l (F)]. Blood level of erythropoietin was related (r = 0.77) to arterial oxygen saturation but not to the levels of progesterone or estradiol. We conclude that erythropoiesis was not altered by menstrual cycle phase during the first days at 4,300-m altitude.

Adult↗
PubMed2001

Clinically silent circulating microemboli in 20 patients with carotid or vertebral artery dissection.

BACKGROUND AND PURPOSE: Carotid and vertebral artery dissections are frequently complicated by cerebral embolism. Detection of clinically silent circulating microemboli by transcranial Doppler sonography (TCD) is now widely investigated in patients with carotid artery disease in the hope to identify patients at increased risk for stroke. METHODS: In 20 patients with carotid (n = 17) or vertebral (n = 2) artery dissection, or both (n = 1), we performed a 1-hour microembolus detection downstream to the dissection in the middle or in the posterior cerebral artery, respectively. RESULTS: Five patients with a carotid artery stenosis of > or = 90% or with carotid artery occlusion showed microembolic signals at a rate of up to 15 events/h. In all these patients, the onset of the dissection was within the last 58 days. Patients with lower degrees of stenosis or onset of symptoms beyond 58 days did not show microembolic signals at all. Three patients who had presented with recurrent ischaemic events prior to TCD monitoring unexceptionally had microembolic signals. CONCLUSION: Microembolic signals occur in patients with high-grade stenosis or occlusion due to acute cervical artery dissection. Patients with microemboli seem to be at increased macroembolic risk, i.e. stroke recurrence, and may require close-meshed clinical follow-up and possibly stronger antithrombotic treatment.

Adult↗
PubMed2000

Evidence for oxidative stress in bronchiolitis obliterans syndrome after lung and heart-lung transplantation. The Munich Lung Transplant Group.

Bronchiolitis obliterans syndrome (BOS) is the most serious long-term sequel of lung or heart-lung transplantation (H/LTX). Neutrophilia in the lower respiratory tract is a prominent feature of BOS. Because polymorphonuclear leukocytes (PMN) are capable of releasing large quantities of reactive oxygen species, we measured indicators of oxidative stress and glutathione levels representing antioxidant defense in H/LTX patients (HLTX, n=6; double-LTX, n=7; single-LTX, n=9). We analyzed 19 bronchoalveolar lavage (BAL) samples from 13 non-BOS patients (nine female, four male: age 39+/-4 years) and 17 BAL samples from nine BOS patients (five female, four male: age 33+/-2 years). PMN were the predominant BAL cell population in BOS (61.7+/-7.8% vs. 12.3+/-3.4%, P<0.001). Myeloperoxidase activity in the epithelial lining fluid and oxidized methionine residues in BAL-derived proteins were elevated in BOS (8.6+/-1.6 U/ml vs. 2.2+/-0.6 U/ml, P<0.01; and 12.6+/-1.1% vs. 7.7+/-0.8%, P<0.001, respectively). In addition, the concentration of reduced glutathione in epithelial lining fluid was decreased in BOS (162.6+/-20.1 microM vs. 345.8+/-57.1 microM, P<0.01), whereas the proportion of oxidized glutathione was increased (13.9+/-2.0O% vs. 6.7+/-1.2%, P<0.001). PMN, myeloperoxidase, and oxidized methionine residues were inversely correlated, whereas reduced glutathione was positively correlated with forced expiratory volume in 1 sec (P<0.05 to P<0.001). We conclude that excessive oxidative stress and a lack of glutathione are associated with BOS after H/LTX and may play relevant roles in the development of this disorder.

Adult↗
PubMed2000

Sympathoadrenal responses to submaximal exercise in women after acclimatization to 4,300 meters.

The purpose of this investigation was to determine the sympathoadrenal response to exercise in women after acclimatization to high altitude. Sixteen eumenorrheic women (age, 23.6 +/- 1.2 years; weight, 56.2 +/- 4.3 kg) were studied at sea level and after 10 days of high-altitude exposure (4,300 m) in either the follicular (n = 11) or luteal (n = 5) phase. Subjects performed two 45-minute submaximal steady-state exercise tests (50% and 65% peak O2 consumption [VO2 peak]) at sea level on a bicycle ergometer. Exercise tests were also performed on day 10 of altitude exposure (50% VO2 peak at sea level). As compared with rest, plasma epinephrine levels increased 36% in response to exercise at 50% VO2 peak at sea level, with no differences found between cycle phases. This increase was significantly greater (increase 44%) during exercise at 65% VO2 peak. At altitude, the epinephrine response was identical to that found for 65% VO2 peak exercise at sea level (increase 44%), with no differences found between phase assignments. The plasma norepinephrine response differed from that for epinephrine such that the increase with exercise at altitude (increase 61%) was significantly greater compared with 65% Vo2 peak exercise at sea level (increase 49%). Again, no phase differences were observed. It is concluded that the sympathoadrenal response to exercise (1) did not differ between cycle phases across any condition and (2) was similar to that found previously in men, and (3) the relative exercise intensity is the primary factor responsible for the epinephrine response to exercise, whereas altitude had an additive effect on the norepinephrine response to exercise.

Adrenal Glands↗
PubMed2000

Women at altitude: carbohydrate utilization during exercise at 4,300 m.

To evaluate the hypothesis that exposure to high altitude would reduce blood glucose and total carbohydrate utilization relative to sea level (SL), 16 young women were studied over four 12-day periods: at 50% of peak O(2) consumption in different menstrual cycle phases (SL-50), at 65% of peak O(2) consumption at SL (SL-65), and at 4,300 m (HA). After 10 days in each condition, blood glucose rate of disappearance (R(d)) and respiratory exchange ratio were measured at rest and during 45 min of exercise. Glucose R(d) during exercise at HA (4.71 +/- 0.30 mg. kg(-1). min(-1)) was not different from SL exercise at the same absolute intensity (SL-50 = 5.03 mg. kg(-1). min(-1)) but was lower at the same relative intensity (SL-65 = 6.22 mg. kg(-1). min(-1), P < 0.01). There were no differences, however, when glucose R(d) was corrected for energy expended (kcal/min) during exercise. Respiratory exchange ratios followed the same pattern, except carbohydrate oxidation remained lower (-23.2%, P < 0.01) at HA than at SL when corrected for energy expended. In women, unlike in men, carbohydrate utilization decreased at HA. Relative abundance of estrogen and progesterone in women may partially explain the sex differences in fuel utilization at HA, but subtle differences between menstrual cycle phases at SL had no physiologically relevant effects.

Adult↗
PubMed2000

Women at altitude: energy requirement at 4,300 m.

To test the hypotheses that prolonged exposure to moderately high altitude increases the energy requirement of adequately fed women and that the sole cause of the increase is an elevation in basal metabolic rate (BMR), we studied 16 healthy women [21.7 +/- 0.5 (SD) yr; 167.4 +/- 1.1 cm; 62.2 +/- 1.0 kg]. Studies were conducted over 12 days at sea level (SL) and at 4,300 m [high altitude (HA)]. To test that menstrual cycle phase has an effect on energetics at HA, we monitored menstrual cycle in all women, and most women (n = 11) were studied in the same phase at SL and HA. Daily energy intake at HA was increased to respond to increases in BMR and to maintain body weight and body composition. Mean BMR for the group rose 6.9% above SL by day 3 at HA and fell to SL values by day 6. Total energy requirement remained elevated 6% at HA [ approximately 670 kJ/day (160 kcal/day) above that at SL], but the small and transient increase in BMR could not explain all of this increase, giving rise to an apparent "energy requirement excess." The transient nature of the rise in BMR may have been due to the fitness level of the subjects. The response to altitude was not affected by menstrual cycle phase. The energy requirement excess is at present unexplained.

Adult↗
PubMed2000

Elevated soluble tumour necrosis factor receptor serum concentrations and short-term mortality in liver cirrhosis without acute infections.

BACKGROUND: Serum concentrations of the soluble 75-kDa tumour necrosis factor receptor (sTNF-R 75) are elevated in patients with severe liver disease and may be linked to mortality as well as to prognostic markers related to clinical outcome and metabolic functions in patients with liver cirrhosis. PATIENTS AND METHODS: We prospectively studied the relation of sTNF-R 75 to Child-Pugh score points and serum markers of bile acid (total serum bile acids and 7alpha-hydroxycholesterol), lignocaine (lignocaine metabolite (MEGX) liver function test results) and albumin metabolism (albumin and prealbumin) in 10 healthy individuals and 30 patients with cirrhosis, all free of acute infections. In patients with cirrhosis mortality was recorded for 15 months. RESULTS: Soluble TNF-R 75 concentrations correlated with Child-Pugh score points (r = 0.440, p = 0.015), MEGX test results (r(S) = -0.604, p < 0.001) and prealbumin (r(S) = -0. 527, p < 0.001) in cirrhosis. Nonsurviving patients had almost threefold higher median sTNF-R 75 concentrations (29 ng/ml) than survivors (11 ng/ml) (p = 0.003). Soluble TNF-R 75 serum concentrations with an optimal cut off > 14 ng/ml were significantly more accurate in predicting patient mortality than Child-Pugh score points in a receiver-operator characteristic curve analysis. CONCLUSION: Soluble TNF-R 75 serum concentrations appear to be a promising new risk factor for mortality in patients with cirrhosis without acute infections.

Adult↗
PubMed2000

A highly sensitive quantitative cytosensor technique for the identification of receptor ligands in tissue extracts.

Because G-protein-coupled receptors (GPCRs) constitute excellent putative therapeutic targets, functional characterization of orphan GPCRs through identification of their endogenous ligands has great potential for drug discovery. We propose here a novel single cell-based assay for identification of these ligands. This assay involves (a) fluorescent tagging of the GPCR, (b) expression of the tagged receptor in a heterologous expression system, (c) incubation of the transfected cells with fractions purified from tissue extracts, and (d) imaging of ligand-induced receptor internalization by confocal microscopy coupled to digital image quantification. We tested this approach in CHO cells stably expressing the NT1 neurotensin receptor fused to EGFP (enhanced green fluorescent protein), in which neurotensin promoted internalization of the NT1-EGFP receptor in a dose-dependent fashion (EC(50) = 0.98 nM). Similarly, four of 120 consecutive reversed-phase HPLC fractions of frog brain extracts promoted internalization of the NT1-EGFP receptor. The same four fractions selectively contained neurotensin, an endogenous ligand of the NT1 receptor, as detected by radioimmunoassay and inositol phosphate production. The present internalization assay provides a highly specific quantitative cytosensor technique with sensitivity in the nanomolar range that should prove useful for the identification of putative natural and synthetic ligands for GPCRs.

Animals↗
PubMed2000

Immunohistochemical localization, biochemical characterization, and biological activity of neurotensin in the frog adrenal gland.

The primary structure of neurotensin has been recently determined for the frog Rana ridibunda (Endocrinology 139: 4140-4146, 1998). In the present study, we have investigated the distribution and biochemical characterization of neurotensin-like immunoreactivity in the frog adrenal gland, using an antiserum directed against the conserved C-terminal region of the peptide. Neurotensin-like immunoreactivity was detected in two populations of nerve fibers: numerous varicose fibers coursing between adrenal cells, and a few processes located in the walls of blood vessels irrigating the gland. Reversed-phase HPLC analysis of frog adrenal gland extracts revealed the existence of a major peak of neurotensin-like immunoreactivity that exhibited the same retention time as synthetic frog neurotensin. The possible involvement of neurotensin in the regulation of steroid secretion was studied in vitro using perifused frog adrenal slices. For concentrations ranging from 10(-10) to 10(-5) M, synthetic frog neurotensin increased corticosterone and aldosterone production in a dose-dependent manner (EC50 = 1.2 x 10(-9) M and 5.8 x 10(-10) M, respectively). Repeated administration of neurotensin induced a reproducible stimulation of steroid output without any tachyphylaxis. Prolonged administration (3 h) of frog neurotensin caused a transient increase in corticosterone and aldosterone secretion followed by a decline of corticosteroid secretion. Neurotensin also produced a significant stimulation of corticosteroid secretion from dispersed frog adrenal cells. This study demonstrates that neurotensin is located in nerve processes innervating the adrenal gland of amphibians. The results also show that synthetic frog neurotensin exerts a direct stimulatory effect on corticosteroid output. Taken together, these data support the view that neurotensin, released by nerve fibers, may act as a local regulator of corticosteroid secretion.

Adrenal Glands↗