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K Lindström

Publications and source records attributed to K Lindström.

At least 127 records · Page 7Linked to original sources

Alpha-adrenoceptor stimulation, but not muscarinic stimulation, increases cyclic AMP accumulation in brain slices due to protein kinase C mediated enhancement of adenosine receptor effects.

In the present study, using rat hippocampal slices, we have further examined the stimulatory effect of alpha 1-adrenoceptors on the accumulation of cyclic AMP, which is known to depend on calcium and adenosine. The addition of noradrenaline (NA) stimulated the accumulation of [3H]inositol phosphates in [3H]inositol-treated slices. This effect was shared by carbachol (10-100 mumol l-1) but not by the adenosine receptor agonist 2-chloroadenosine (100 mumol l-1). The stimulatory effect of the alpha-agonists (phenylephrine or NA + propranolol) on cyclic AMP was shared by a diacylglycerol derivative, sn-1-oleyl-2-acetyl glycerol (OAG), and by the tumour-promoting phorbol esters phorboldibutyrate (PDiBu) and tetradecanoyl phorbol acetate (TPA). PDiBu caused a translocation of protein kinase C from soluble to particulate fractions. The effects of PDiBu and alpha-adrenoceptor stimulation on cyclic AMP were not additive. Surprisingly, carbachol (1-1000 mumol l-1) did not stimulate cyclic AMP accumulation in rat hippocampal slices either in the presence or in the absence of an adenosine receptor agonist. The results are compatible with the opinion that alpha-adrenoceptor stimulating drugs enhance the formation of inositol phosphates and diacylglycerol, which synergistically activate protein kinase C, which in turn augments the stimulation of cyclic AMP formation. Thus, a neurotransmitter whose principal biological effect is to stimulate inositol phosphate formation can influence cyclic AMP formation by virtue of an interaction with the actions of the ubiquitous neuromodulator adenosine. The fact that the effect of the alpha-receptor stimulation was not mimicked by a muscarinic agonist could indicate that other factors besides activation of inositol phospholipid hydrolys are important for this receptor-receptor interaction.

Adrenergic alpha-Agonists↗

Release of endogenous and radioactive purines from the rabbit retina.

The adenine nucleotide pool of rabbit retina was labeled by an intravitreal injection in vivo of [3H]adenosine. Practically all the radioactivity was retained in the form of adenine nucleotides. The relative proportion of [3H]adenine nucleotides was the same as that of endogenous nucleotides. Potassium depolarization (43.6 mM) in vitro caused a rapid increase in the rate of release of radioactive purines. The radioactive material was composed of hypoxanthine, xanthine, inosine and trace amounts of adenine, adenosine and adenine nucleotides. The release of radioactive purines was delayed and reduced by the addition of the nucleoside inhibitor dipyridamole suggesting that the purines may be released in the form of nucleosides. Similarly, the addition of the ecto 5'-nucleotidase inhibitor alpha, beta-methylene ADP (AOPCP) did not alter the release of radioactivity or the composition of the released purines. Endogenous hypoxanthine, xanthine and inosine could be detected in the effluents, but there was only a very modest increase following potassium depolarization. There was a slight, but significant, decrease in the release of endogenous adenosine and increase in AMP after AOPCP. It is concluded that there is an intensive uptake and phosphorylation of adenosine in the rabbit retina. Depolarization induces release of radioactive purine nucleosides and bases. Most of these compounds appear to be released as such, but in addition there may be a small (maximally a few per cent of the total) fraction of the purines that are released as nucleotides.

Adenine↗

Effect of adenosine receptor agonists and other compounds on cyclic AMP accumulation in forskolin-treated hippocampal slices.

The effect of adenosine analogues and some putative neurotransmitters have been studied on cyclic AMP accumulation in rat hippocampal slices treated with the adenylate cyclase activator forskolin. The effects of PGE2 and histamine were potentiated by forskolin (0.1 microM). Isoprenaline and NECA had essentially additive effects with 0.1 microM forskolin and serotonin (above 10(-4) M) inhibited forskolin-stimulated cyclic AMP accumulation. The A1-adenosine receptor selective adenosine analogue R-PIA inhibited forskolin stimulated cyclic AMP accumulation in low doses and stimulated in high. NECA, adenosine and 2-chloroadenosine uniformly stimulated cyclic AMP accumulation. 2',5'-dideoxyadenosine inhibited, but only at high concentrations. Both the stimulatory and the inhibitory effects of R-PIA were antagonized by 8-phenyltheophylline (10 microM). Enprofylline (100 microM) selectively inhibited the stimulatory effect. In the presence of enprofylline both 2-chloroadenosine showed an inhibitory effect on cyclic AMP accumulation. It is concluded that the forskolin-treated rat hippocampal slice is a useful preparation to study both stimulatory and inhibitory effects of transmitters and modulators on adenylate cyclase. The results also show that the rat hippocampus has both A1-receptors that are linked to inhibition of cyclic AMP accumulation and A2-receptors that are linked to stimulation. Furthermore, enprofylline is shown to selectively antagonize the stimulatory response, revealing inhibitory effects of compounds such as 2-chloroadenosine and adenosine.

2-Chloroadenosine↗

The xanthine derivative 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) enhances the actions of adenosine.

The effect of two closely related xanthine derivatives, pentoxifylline and HWA 285, on cyclic AMP accumulation in rat hippocampal slices and on adenosine uptake in erythrocytes was examined. Pentoxifylline was a weak competitive antagonist of adenosine effects on cyclic AMP accumulation. HWA 285, by contrast, had a small stimulatory effect per se and also potentiated the effect of adenosine (10-30 microM). Neither pentoxifylline nor HWA 285 significantly affected the cyclic AMP accumulation induced by the stable adenosine analogue NECA or by alpha- or beta-adrenoceptor activation. HWA 285 was a much more potent inhibitor of adenosine uptake into human erythrocytes than pentoxifylline and other examined xanthines including thiocaffeine, 8-p-sulphophenyltheophylline, theophylline, caffeine and enprofylline. It is suggested that HWA 285 may potentiate, rather than antagonize, the effects of endogenous as well as exogenous adenosine, partly as a consequence of adenosine uptake inhibition.

Adenosine↗

Treatment with N-ethylmaleimide selectively reduces adenosine receptor-mediated decreases in cyclic AMP accumulation in rat hippocampal slices.

N-ethylmaleimide (NEM) has been reported to interact with the GTP-binding Ni-protein; we have examined its effect on adenosine receptor binding in feline cortical membranes and on adenosine-receptor mediated effects on cyclic AMP accumulation in rat hippocampal slices. Treatment of cortical membranes with NEM (100 microM for 5 min) altered the binding of [3H]-phenylisopropyladenosine (PIA) from being almost exclusively to a single class of high affinity sites (KD = 1.65 nM) to binding at two classes of sites (KDH = 2.1 nM, KDL = 102 nM). The total number of binding sites was similar (825-845 fmol mg-1 in control membranes, 944-1428 fmol mg-1 in NEM-treated membranes). In rat hippocampal slices treated with forskolin (0.3 microM) L-PIA produced a biphasic effect on cyclic AMP accumulation: an inhibition at 0.03 to 1 microM and at higher concentrations, a stimulation. Treatment with 50 microM NEM selectively inhibited the inhibitory phase, causing stimulation at lower concentrations of L-PIA. At 50 microM, NEM did not alter basal or forskolin-stimulated cyclic AMP accumulation but at higher concentrations inhibition was observed. It is concluded that NEM can, in certain doses, selectively block adenosine A1-receptor-mediated effects without affecting A2-receptor-mediated actions in the same tissue. It is suggested that this is due to NEM affecting the Ni guanine nucleotide binding protein.

Animals↗

Actions of enprofylline in the rat hippocampus.

Enprofylline is a novel xanthine with a low adenosine antagonistic potency, but with a good bronchodilator activity. In order to further elucidate its central nervous actions we have studied its effects in the rat hippocampus, both electrophysiologically and biochemically. Adenosine was found to depress evoked field excitatory post-synaptic potentials (EPSPs) in the rat hippocampus. The effect of adenosine was antagonized by theophylline but not by enprofylline. Both xanthines caused a slight increase per se of the field EPSP amplitude. Cyclic AMP accumulation in the rat hippocampus was stimulated by the adenosine analogue NECA, by isoprenaline and by noradrenaline in the presence of propranolol. The cyclic AMP accumulation induced by these agents was not significantly altered by omitting calcium. Enprofylline antagonized the effect of NECA and noradrenaline (after beta-blockade) but not that of isoprenaline. The IC50 of enprofylline against NECA was about 20 mumol X 1(-1). The inhibitory effect of enprofylline against NECA induced cyclic AMP accumulation was not affected by omitting calcium or by the calcium channel antagonist felodipine, but was decreased by the calmodulin inhibitor stelazine and the intracellular calcium chelator Quin-2. The results show that enprofylline is much more potent as an inhibitor of adenosine A2-receptor-mediated cyclic AMP accumulation than against adenosine A1-receptor-mediated inhibition of field EPSP. The difference may depend on a role of a special pool of calcium in the former response.

Adenosine↗

Levels of adenosine and adenine nucleotides in slices of rat hippocampus.

ATP, ADP, AMP, IMP, adenosine, inosine and cyclic AMP were measured in slices of the rat hippocampus maintained in vitro. Immediately following cutting ATP was low (3.5 +/- 0.6 nmol/mg protein) and AMP high (8.6 +/- 0.9 nmol/mg), giving an energy charge of only 0.34 +/- 0.02. Over the next 90 min the energy charge gradually normalized (to 0.92 +/- 0.01), partly due to conversion of AMP to ATP, but mainly to breakdown to adenosine and other purines which were recovered in the incubation medium. Total purine content decreased from approximately 18 to 10 nmol/mg protein in the first hour following cutting. In slices from old rats the energy charge was lower 60 min following preparation than in younger rats, while cyclic AMP and adenosine levels were higher. The adenosine antagonist 8-phenyl-theophylline tended to enhance the recovery of responsiveness after preparation of the slices. Stimulation of excitatory afferent fibers at a frequency of 10 Hz for 5 min did not significantly alter the purine levels in brain slices, while hypoxia decreased the energy charge significantly and tended to increase adenosine levels. These changes occurred somewhat later than the fall in electrophysiological responsiveness. 8-Phenyl-theophylline was able to delay somewhat the decline in the amplitude of synaptic responses under hypoxic conditions. It is concluded that the viable part of the hippocampal slice, which accounts for about half of the tissue, has levels of adenine nucleotides and adenosine which are similar to those found in the intact rat brain. The return of electrophysiological function following slice preparation is paralleled by a normalization of the energy charge, the adenosine level and the concentration of cyclic AMP. The absence of electrophysiological activity following cutting, and the decreases in such responses following either prolonged afferent stimulation or hypoxia may be related to changes in purine concentration in the slice. Although adenosine accumulating in the slice may contribute to the depression of electrophysiological responses it is probably not the major factor responsible for the reduction in synaptic responsiveness.

Adenine Nucleotides↗

Dynamics of a continent caecal reservoir for urinary diversion.

Motor activity of the caecal reservoir for urine, and of the intussuscepted nipple valve in the ileal outlet, was studied in seven continent and two incontinent patients by means of a catheter equipped with two microtransducers. The basal pressure was low in the reservoir even at large-volume filling. In the continent patients the basal pressure was always higher in the ileal outlet than in the reservoir. No high-pressure zone was present in the outlet in the incontinent patients. Intermittent pressure waves occurred in the reservoir, and they increased in frequency, duration and amplitude with increasing filling. Pressure waves with higher amplitude arose simultaneously in the outlet. Increasing time from construction of the reservoir was accompanied by decreasing amplitude of the pressure waves, indicating adaptation towards the larger functional capacity of the reservoir. The recorded dynamics seemed to reflect the functional state of the reservoir.

Adult↗

Physiological characteristics of diameter pulses in the fetal descending aorta.

A study was performed to establish the dynamic behavior in situ of the descending aorta in the human fetus. The pulsatile movements of the vessel walls were recorded in 36 clinically normal fetuses using a real-time phase-locked ultrasonic system measuring echo movements with high spatial and temporal resolution. The mean amplitude of the diameter pulsations was similar in the 28th - 35th week to that in the 36th - 40th week but, as the apparent diastolic diameter increased, the pulse-elicited increment of the cross-sectional area was 29% larger in the older group. The diastolic diameter decreased (p less than 0.001) and the amplitude of the diameter pulsation increased (p less than 0.001) with prolongation of the previous beat interval. The diameter pulse velocity was positively correlated to gestational age (p less than 0.001), ranging between 1.35 and 2.89 m/sec. The incremental phase of the pulse curve diminished in duration with increasing distance from the heart (p less than 0.001) and with decreasing duration of the previous beat interval (p less than 0.001). The maximum slope of the incremental phase was higher in the more distal part of the aorta (p less than 0.001). The study demonstrates that the diameter pulses contain useful information on the cardiovascular dynamics and provides evidence that the Frank-Starling mechanism is effective also in the human fetus.

Aorta, Abdominal↗

Occupational solvent exposure and neuropsychiatric disorders.

Long-term exposure to solvents has been shown to induce neuropsychiatric disorders in workers. In this case-referent study the cases comprised 374 construction workers who had been awarded a disability pension due to a neuropsychiatric disorder in 1978-1980. Their matched referents were selected from construction workers who had been granted a pension due to o ther diseases in the same three-year period. The results of this study indicate that solvent exposure increases the risk of being prematurely pensioned due to neuroses, but early pensioning due to alcoholism or other neuropsychiatric disorders is not increased by solvent exposure. This same conclusion has been reached in earlier studies on this matter in other countries.

Adult↗

On the mechanism by which methylxanthines enhance apomorphine-induced rotation behaviour in the rat.

Methylxanthines, such as caffeine and theophylline, potentiate the rotation behaviour induced by dopamine receptor agonists in rats with unilateral lesions of the nigro-striatal pathway. In the present study we have examined the possibility that interaction with central adenosine mechanisms could influence rotation behaviour. Under in vitro conditions adenosine and N6-phenylisopropyl-adenosine (PIA) stimulate cyclic AMP accumulation. This effect was enhanced by the phosphodiesterase inhibitor rolipram, but blocked by alkylxanthines such as caffeine, theophylline and, particularly, 8-phenyl-theophylline. Rotation behaviour induced by apomorphine (0.05 mg/kg), was inhibited by PIA and rolipram and by a low dose of the adenosine deaminase inhibitor EHNA (2 mg/kg). By contrast, theophylline and 8-phenyl-theophylline caused a potentiation. The former drug stimulated rotation behaviour per se, while the latter did not. 8-Phenyl-theophylline entered the brain poorly and its concentration in brain it was less than 1/10 of theophylline. It is concluded that theophylline does not potentiate rotation behaviour secondarily to inhibition of phosphodiesterase. Antagonism of endogenous adenosine may partly explain the effect of methylxanthines. Possibly, some as yet unknown mechanism may also contribute to the effects of xanthine-derivatives on rotation behaviour.

Adenosine↗

Psychological function changes among maintenance house painters exposed to low levels of organic solvent mixtures.

The adverse psychological effects of long-term exposure to organic solvent mixtures were studied among 219 maintenance house painters. Their mean age was 42 years and the duration of exposure 22 years. 229 reinforcement workers of the same mean age served as a nonexposed reference group. The groups were also matched according to pre-exposure intellectual level. The painters average exposure to white spirit was estimated to be 40 ppm. The maintenance house painters were characterized by defects in short-term visual memory and prolonged simple reaction times. Some slight relationships were found between low test performances and various individual indices of long-term exposure to solvents. The results implied that adverse psychological effects existed even though the exposure level was much lower than the hygienic standard applied for white spirit in many countries.

Adult↗

The effect of some drugs with purported antianoxic effect on veratridine-induced purine release from isolated rat hypothalamic synaptosomes.

Several drugs claimed to protect against anoxic damage to the brain and/or to aleviate symptoms of senility were tested for their ability to influence purine overflow from hypothalamic synaptosomes. Theophylline did not influence the total purine release but tended to decrease the nucleoside and increase the nucleotide release. Cyclic nucleotide phosphodiesterase inhibitors were ineffective, whereas drugs that inhibit carrier mediated nucleoside transport inhibited veratridine-induced purine release. Some ergot derivatives, some vinca-analogues and the vasodilator ifenprodil also decreased stimulated purine release, but their effect could not be attributed to adenosine transport inhibition. The results suggest that drugs are reported to aleviate symptoms of anoxic damage or senility may inhibit the release of adenosine and related compounds in the central nervous system. Some possible reasons why a decreased purine release may protect against ischaemic brain damage are discussed.

Animals↗

Airborne ultrasound applied to anthropometry--physical and technical principles.

Airborne ultrasound has been utilized for remote measurement of distance, direction, size, form, volume and velocity. General anthropometrical measurements are performed with a newly constructed real-time linear array scanner. To make full use of the method, we expect a rapid development of high-frequency ultrasound transducers for use in air.

Anthropometry↗