Biomedical subjects

K K Skrede

Publications and source records attributed to K K Skrede.

17 recordsLinked to original sources

PubMed1996

Peritoneal leucocytes from spontaneously hypertensive rats have reduced chemiluminescence response and lowered sensitivity to dexamethasone in vivo.

The genetically altered hypothalamo-pituitary-adrenocortical axis in the spontaneously hypertensive rat (SHR) suggests altered phagocyte function in this strain. We therefore compared luminol-amplified chemiluminescence in peritoneal leucocytes from 10- to 12-week-old SHRs and age-matched Wistar-Kyoto rats (WKYs) activated by serum-opsonized zymosan particles (SOZ), N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). While the number of peritoneal monocytes/macrophages was increased by 49% in SHRs relative to WKYs, activator-induced chemiluminescence per cell in SHRs was only 14-42% of that in WKYs. FMLP responses were especially low in SHRs. Treatment of rats with dexamethasone in the drinking water for 48 h prior to ex vivo experiments reduced chemiluminescence dose-dependently in WKYs as well as in SHRs. ED50 of dexamethasone in SHRs was, however, increased compared to WKYs, indicating lowered sensitivity to dexamethasone in SHRs. No evidence was found of strain differences in differential distribution of peritoneal cells or in pharmacokinetics of dexamethasone. Plasma ACTH levels were significantly higher in SHRs than in WKYs, while basal plasma corticosterone concentrations in SHRs and WKYs were not significantly different. The results suggest that production of reactive oxygen compounds by peritoneal mononuclear phagocytes is reduced in SHRs compared with WKYs, and that the phagocyte respiratory burst is modulated differently by endogenous glucocorticoids in the two strains. We propose that reduced activity of the phagocyte NADPH oxidase-myeloperoxidase system is a major contributory cause of the altered chemiluminescence responses in SHRs. The data indicate that species differences may also be present at earlier steps in the signal transduction pathways activated by SOZ, fMLP and PMA.

Adrenocorticotropic Hormone↗

PubMed1995

Dexamethasone and methylprednisolone affect rat peritoneal phagocyte chemiluminescence after administration in vivo.

Production of reactive oxygen compounds by peritoneal monocytes/macrophages was studied in rats exposed to dexamethasone or methylprednisolone in the drinking water. Luminol-amplified chemiluminescence was measured in preparations of peritoneal leukocytes activated ex vivo by serum opsonized zymosan, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). After dexamethasone administration for 1 day (approximately 0.13 mg/kg per 24 h) a significant reduction in chemiluminescence was found in cells stimulated with serum opsonized zymosan, while responses to fMLP and PMA stimulation were significantly reduced after 2 days. The maximal inhibition obtained after 5-8 days of dexamethasone administration (plasma levels < 5 nM) was 92.0 +/- 1.2%, 87.6 +/- 0.2% and 84.5 +/- 3.1% in cells stimulated with serum opsonized zymosan, fMLP and PMA, respectively. Administration of dexamethasone or methylprednisolone for 48 h gave a dose-dependent reduction of chemiluminescence. ED50 values of dexamethasone were estimated at 0.06-0.15 mg/kg for the different stimulators (plasma concentrations 5-10 nM). Estimated ED50 values for methylprednisolone were 35-36 mg/kg. Since the percentage of mononuclear phagocytes in the peritoneal cell population did not change significantly with dose or time of dexamethasone exposure, this study indicates that glucocorticoids have a depressive effect on the monocyte/macrophage 'respiratory burst' in vivo. The results are consistent with the hypothesis that these effects are mediated by glucocorticoid receptors. Although the pathway activated by serum opsonized zymosan was more rapidly inhibited than the fMLP- and PMA-activated pathways, the responses induced by the different stimulators were similarly affected, suggesting a modulation of common components in the activation pathways, possibly protein kinase C or the NADPH-oxidase complex, after administration of low pharmacological doses of glucocorticoids in vivo.

Animals↗

PubMed1995

Effect of in vivo corticosterone and acute food deprivation on rat resident peritoneal cell chemiluminescence after activation ex vivo.

Adrenoglucocorticoid regulation of rat peritoneal monocyte/macrophage function was studied by exposing rats to corticosterone (CS) in the drinking water, and to fast (48 h). Production of reactive oxygen metabolites was measured by luminol amplified chemiluminescence (CL) in preparations of peritoneal cells activated by serum treated zymosan (STZ). Administration of CS which led to an increase in plasma CS from 31 (controls) to 46 ng mL-1, reduced CL (per cell) by 31%. Fast, which did not change plasma CS or ACTH, also had an inhibitory effect on CL (-25%), while the combination of CS administration and fast strongly inhibited the CL (-89%), indicating that plasma CS and fast reduced CL in a synergistic way. Similar effects on cell number were observed: CS-administration, fast and the combination reduced macrophage numbers (-13, -19.7 and -55%), while no significant effect was observed on the number of monocytes. The effect of adrenalectomy (adx) was studied in another series of experiments; adx induced no significant change in peritoneal leucocyte number or composition, while cells from adx animals had significantly higher chemiluminescence reaction than cells from sham operated animals. CS substitution in adx animals reduced CL by 30% while sham operated animals had 49% lower CL in adx. The data from adx animals also suggest that endogenous levels of CS are inhibitory for CL, but the results are not conclusive for the effect of very low doses of CS since other mechanisms than elimination of CS could prime the chemiluminescence reaction after adx. In conclusion, a moderate elevation of CS after systemic administration in vivo reduced the total number of mononuclear phagocytes in rat peritoneum, reduced the relative number of macrophages compared with monocytes, and suppressed the function of monocytes/macrophages by reducing the production of reactive oxygen molecules in activated cells. Furthermore, the effect of corticosterone was also dependent on the physiological situation, since the effects of fast and corticosterone were synergistic.

Adrenalectomy↗

PubMed1994

Atrial natriuretic peptide in plasma after prolonged physical strain, energy deficiency and sleep deprivation.

Plasma concentrations of atrial natriuretic peptide (ANP) were investigated daily in 16 male cadets during a 6-day military training course with continuous heavy physical activities, sleep and energy deficiency (course I). At the end of another similar course (course II) 15 cadets were studied during 30-min cycle exercise at 50% maximal oxygen uptake with and without glucose infusion. A small, but not significant increase was found in the plasma concentrations of ANP during course I from 9.6 (SEM 1.1) pmol.l-1 in the control experiment to 11.1 (SEM 0.5) pmol.l-1 on day 5. During course II a small but significant increase was found from 7.8 (SEM 0.5) pmol.l-1 in the control experiment to 9.1 (SEM 0.5) pmol.l-1 at the end of the course. Plasma osmolality and chloride concentration decreased during the course. During the exercise test a significant increase was seen in ANP concentration from 8.2 (SEM 0.8) to 13.1 (SEM 2.0) pmol.l-1 in the control experiment and from 9.4 (SEM 0.7) to 13.5 (SEM 1.2) pmol.l-1 during the course. This response was attenuated by glucose infusion, an effect which may have been due to an exercise induced increase in plasma chloride concentration being abolished. In contrast, the potassium concentration response to exercise was increased during the course but unaffected by glucose infusion. In conclusion, the large increases in endogenous plasma catecholamine concentration shown to take place during previous courses were not reflected in the plasma concentrations of ANP, indicating only a moderate cardiac stress or no cardiac work overload during such courses.

Adult↗

PubMed1994

Adrenaline stimulated cyclic adenosine monophosphate response in leucocytes is reduced after prolonged physical activity combined with sleep and energy deprivation.

The mechanism for adrenergic desensitisation during physical stress was studied by measuring [125I] cyanopindolol ([125I]CYP) binding sites and the adrenaline stimulated cyclic adenosine monophosphate (cAMP) responses in peripheral blood leucocytes from ten male cadets during a 5-day military training course. The cadets had physical activities around the clock corresponding to a daily energy consumption of about 40,000 kJ but with an intake of only 2,000 kJ, and only 1-3 h of sleep in the 5 days. During the course, the maximal cAMP response to adrenaline stimulation was reduced to about 45% in granulocytes and to 52% in mononuclear cells, and the half maximal response was obtained only at 5-10 times higher adrenaline concentrations than in the control experiment. The binding sites for [125I]-CYP in mononuclear cells increased during the course. However, [125I]-CYP measured not only surface receptors but also intracellular receptors and might even have represented other binding sites. In conclusion, this study showed that decreased cAMP response to adrenergic stimulation would seem to be one of the mechanisms behind adrenergic desensitisation during stress.

Adrenergic beta-Antagonists↗

PubMed1981

Increased resting and evoked release of transmitter following repetitive electrical tetanization in hippocampus: a biochemical correlate to long-lasting synaptic potentiation.

In vitro stimulation of two axonal branches from hippocampal CA3 pyramids, the CA1 afferent Schaffer collaterals and the CA3 efferents to septum through fimbria, released D-[3H]aspartate as a measure for endogenous L-glutamate. Following bursts of repetitive electrical stimuli to the Schaffer collaterals, a long-lasting and significantly increased resting efflux, as well as an increased stimulus evoked release of D-aspartate, appeared. No such persistent increase in D-aspartate efflux was recorded from the septal terminals. We propose that increased transmitter liberation may account for long-term synaptic potentiation in hippocampus.

Animals↗

PubMed1981

Differential release of D-[3H]aspartate and [14C]gamma-aminobutyric acid following activation of commissural fibres in a longitudinal slice preparation of guinea pig hippocampus.

Low-stimulus frequencies released both D-[3H]aspartate and [14C]GABA in double labelling experiments after activation of the commissural fibres to stratum oriens in hippocampal slices. The stimulus-dependent release of [14C]GABA was highest at low stimulus frequencies (10 Hz) whereas at higher stimulus frequencies (30--50 Hz) it was almost abolished. All stimulus frequencies used released D-[3H]aspartate. The results indicate that activation of the commissural fibres in stratum oriens, using low stimulus frequencies, activates pyramidal cells which stimulate inhibitory neurones releasing GABA as a transmitter.

Animals↗

PubMed1980