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G von Euler

Publications and source records attributed to G von Euler.

At least 37 records · Page 2Linked to original sources
PubMed1995

Persistent, specific and dose-dependent effects of toluene exposure on dopamine D2 agonist binding in the rat caudate-putamen.

Exposure to toluene (40-320 ppm; 4 weeks, 6 h/day, 5 days/week), followed by a postexposure period of 29-40 days, decreased the wet weight of the caudate-putamen and of the subcortical limbic area (maximal effect of 10% attained at 80 ppm toluene) of the male rat. Furthermore, toluene exposure decreased the IC50 values (significant effects attained at 80 ppm), the KH, the KL, and the RH% values of dopamine on [3H]raclopride-binding in the caudate-putamen. Toluene exposure did not significantly affect either the body weights, the wet weights of the whole brain, the serum prolactin levels, the KD or the Bmax values of [3H]raclopride-binding in the caudate-putamen and the subcortical limbic area, or the IC50 values of dopamine at [3H]raclopride-binding sites in the subcortical limbic area. Exposure to xylene or styrene (80 and 40 ppm, respectively; 4 weeks, 6 h/day, 5 days/week), followed by a postexposure period of 26-32 days, had no effect on the parameters described above (prolactin levels were not analyzed). The present study indicates that long-term exposure to low concentrations of toluene (> or = 80 ppm), but not xylene (80 ppm) or styrene (40 ppm), leads to persistent increases in the affinity of dopamine D2 agonist binding in the rat caudate-putamen.

Aging↗
PubMed1995

Regional and age-dependent differences in the affinity of dopamine D2 agonist binding in the rat brain.

In sagittal brain sections of newborn male rats (1-day-old) there were no regional differences in the IC50 values of dopamine at [125I]iodosulpride binding sites. In contrast, in 20- and 60-day-old rats, there was a selective increase in the IC50 values of dopamine in the nucleus accumbens, caudate-putamen, and olfactory tubercule. The IC50 values of these regions decreased in 262-day-old rats. Some of the other brain areas appeared to behave in a similar, but much less pronounced, fashion. Thus, there were significant regional differences in the IC50 values of young, adult, and old rats. In addition, there was a rapid increase in [125I]iodosulpride binding between the newborn and the 20-day-old rats, which leveled off thereafter, and selectively decreased in the substantia nigra of the 262-day-old rats. In conclusion, these results indicate that a biphasic decrease-increase in the affinity of D2 agonist binding sites occurs selectively in the basal ganglia. These findings may be of relevance for developmental diseases in which dopaminergic mechanisms have been implicated, such as schizophrenia and Parkinson's disease.

Aging↗
PubMed1994

Chronic nicotine treatment counteracts dopamine D2 receptor upregulation induced by a partial meso-diencephalic hemitransection in the rat.

To further elucidate the previously demonstrated protective actions of nicotine on lesioned nigrostriatal dopamine (DA) systems (Janson and Møller, Neuroscience, 57 (1993) 931-941), the present receptor binding experiments were carried out. Rats were partially hemitransected at the meso-diencephalic junction and the effects of chronic continuous (-)nicotine treatment (osmotic pumps s.c., 0.125 mg/kg/h, 14 days) on [3H]N-propylnorapomorphine ([3H]NPA) and [3H]methylcarbamylcholine ([3H]MCC) binding were investigated in striatal coronal sections to study the agonist binding sites of DA D2 receptors and nicotinic cholinoceptors, respectively. In saline-treated but not in nicotine-treated rats, the lesion led to an increased Bmax value of [3H]NPA binding. The Bmax value of [3H]MCC binding was increased by nicotine treatment and decreased by the partial hemitransection. These results indicate that chronic nicotine treatment counteracts the lesion-induced upregulation of the high-affinity agonist binding site of the DA D2 receptor, which may be explained by an increased presence of DA via a protective effect of nicotine on neostriatal DA terminals. This action of nicotine may be of interest in the treatment of neurodegenerative diseases such as Parkinson's disease.

Animals↗
PubMed1994

Modulation of dopamine D3 receptor binding by N-ethylmaleimide and neurotensin.

GTP or G protein inactivation by N-ethylmaleimide reduced the Bmax value but not the KD value of 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT) binding in the rat subcortical limbic area. Neurotensin (10 nM) increased the KD and the Bmax values of [3H]7-OH-DPAT binding, and these effects persisted also following N-ethylmaleimide pretreatment. N-Propylnorapomorphine, quinpirole, raclopride, and remoxipride inhibited [3H]7-OH-DPAT binding with Ki values of 0.093, 1.97, 10.6, and 710 nM, respectively. These findings indicate that the D3 receptor is coupled to G proteins in the brain, and that neurotensin can modulate D3 agonist binding by a G protein-independent mechanism.

Animals↗
PubMed1994

Persistent effects of 80 ppm toluene on dopamine-regulated locomotor activity and prolactin secretion in the male rat.

Neurotoxicology 15(3): 621-624, 1994. In the present study we have investigated the effects of toluene exposure (80 ppm, 4 weeks, 5 day/week, 6 h/day) on the serum levels of prolactin, and elaborated our earlier findings about persistent effects of toluene exposure on apomorphine-induced (1 mg/kg, s.c.) locomotor activity. We found that the serum levels of prolactin were increased by 67% in the toluene-exposed rats, as analyzed 17 days after the last exposure. The locomotor activity counts of the control rats were not normally distributed before log-transformation, since most rats showed a low level of activity and only a few showed a very high activity level. The toluene-exposed rats showed a higher level of apomorphine-induced locomotion and motility but not rearing, as analyzed 17 days after the last exposure, whereas spontaneous locomotor activity was unaffected. These results indicate that subacute exposure to 80 ppm of toluene causes persistent impairments in dopamine-mediated neurotransmission.

Animals↗
PubMed1993

Neuromedin N is a potent modulator of dopamine D2 receptor agonist binding in rat neostriatal membranes.

In the concentration range of 1-10 nM, neuromedin N produced a significant concentration-related increase in the Kd values of [3H]L-(-)-N-propylnorapomorphine binding sites in rat neostriatal membranes with a peak action at 10 nM (36% increase versus the control group mean value). The Bmax values were not affected by neuromedin N. Neurotensin at 10 nM induced an increase in the Kd values, which was not affected by a threshold concentration of neuromedin N (0.1 nM). In view of the higher potency of neuromedin N versus neurotensin to modulate neostriatal D2 receptors in contrast to the higher potency of neurotensin versus neuromedin N to bind to the cloned neurotensin receptors, it seems possible that the neuromedin N activated neostriatal neurotensin receptors controlling the D2 receptors represent a distinct subtype of neurotensin receptors.

Animals↗
PubMed1993

Glutamate and glycine decrease the affinity of [3H]MK-801 binding in the presence of Mg2+.

The NMDA receptor is coupled to a cation-selective ion channel, which has been implicated in important brain functions such as long-term potentiation and burst firing, and in neuronal death associated with stroke and epilepsy. We have investigated the binding properties of [3H]MK-801, which binds selectively to the open state of the NMDA channel, at physiological concentrations of Mg2+ in membrane preparations of the rat cerebral cortex. Glutamate and glycine were found to enhance [3H]MK-801 binding at low concentrations and inhibit [3H]MK-801 binding at high concentrations. The inhibition of [3H]MK-801 binding was due to an enhancement of the dissociation rate constant and was reversed by competitive glutamate and glycine antagonists. These findings could be explained by a glutamate- and glycine-induced decrease in the affinity of [3H]MK-801 binding sites within activated NMDA channels, in the presence of Mg2+. This decrease in [3H]MK-801 affinity may correspond to a decreased affinity of the site where Mg2+ causes a voltage-dependent block of the NMDA channel.

Animals↗
PubMed1993

Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat.

The effects of subchronic inhalation exposure to toluene (80 ppm, for 4 weeks, 5 days/week, 6 h/day) was studied on spatial learning (postexposure days 3-6) and memory (postexposure day 14) using a water maze, on spontaneous and apomorphine-induced (1 mg/kg, subcutaneously (s.c.)) locomotor activity (postexposure day 17) and on the binding parameters of the dopamine D2 agonist S(-)[N-propyl-3H(N)]propylnorapomorphine ([H]NPA) in membrane preparations of the neostriatum of the rat. Toluene treatment was found to cause a statistically significant impairment in acquisition and retention of the spatial learning task. Furthermore, toluene significantly increased (2-fold) apomorphine-induced locomotion and caused a trend for a 50-60% increase in motility without any significant effect on rearing. Spontaneous locomotion, motility and rearing were not affected by toluene. Toluene treatment produced a significant 30-40% increase in the Bmax values of [3H]NPA and a trend for a 20-30% increase in the KD values. These results indicate that subchronic exposure to toluene in low concentrations causes a slight but persistent deficit in spatial learning and memory, a persistent increase in dopamine-mediated locomotor activity and an increase in the number of dopamine D2 receptors in the rat.

Administration, Inhalation↗
PubMed1993

Intramembrane receptor-receptor interactions: integration of signal transduction pathways in the nervous system.

During recent years a large number of observations have been made indicating that neuropeptides and other transmitters in various brain areas can regulate the affinity of monoamine receptors via the activation of their own receptors. These "receptor--receptor interactions" can either take place at the plasma membrane level or use intracytoplasmatic loops. This review is mainly focused on the evidence for hetero-regulation of dopamine (DA) D2 receptors in the basal ganglia. The existence of such receptor--receptor interactions increases the plasticity of transmission and opens up the possibility of developing new drugs which indirectly modulate receptor recognition and decoding processes. This would avoid the use of direct receptor agonists or antagonists which induce major side effects such as tolerance and abstinence. Disturbances in the receptor--receptor interactions, including DA D2 receptors, may be involved in the development of neurological and mental diseases such as schizophrenia.

Animals↗
PubMed1992

The glutamate- and glycine-induced reduction of [3H]MK-801 binding in the presence of Mg2+ is reversed at low pH.

At normal pH, glutamate and glycine are known to inhibit [3H]MK-801 binding in the presence of Mg2+. We found, however, that at pH 5.4 glutamate and glycine enhance [3H]MK-801 binding in rat cerebrocortical membranes. Furthermore, H+, similarly to Mg2+, inhibited basal [3H]MK-801 binding. These results indicate that H+ competes with binding sites for Mg2+ and [3H]MK-801, and may be correlated to the depression in neuronal activity observed during acidosis.

Animals↗
PubMed1992

Coactivation of dopamine D1 and D2 receptors increases the affinity of cholecystokinin-8 receptors in membranes from post-mortem human caudate-putamen.

The effects of dopamine in vitro were investigated on the binding sites for cholecystokinin-8 (sulphated, CCK-8) and neurotensin in membrane preparations of the caudate-putamen and nucleus accumbens of post-mortem human brains. Dopamine reduced the IC50 value of competition curves with CCK-8 for [125I]CCK-8 binding in membranes from the caudate-putamen, but not the nucleus accumbens, with a maximal decrease of -25 +/- 9% at 300 nM of dopamine. This decrease could be antagonized by 100 nM of SCH 23390 or 100 nM of raclopride. Kinetic analysis of [125I]CCK-8 binding showed a decrease in the first order dissociation rate constant and in the kinetic Kd (-22 +/- 6% and -24 +/- 6%, respectively) at 300 nM of dopamine, without any significant effect on the apparent or actual association rate constant. Competition curves with neurotensin versus [125I]neurotensin were not affected by dopamine (10-1000 nM) in membranes from the caudate-putamen or the nucleus accumbens. These results suggest that dopamine, by synergistic stimulation of both D1 and D2 receptors, selectively increases the affinity of CCK-8 receptors in the human caudate-putamen, by a selective inhibition of ligand dissociation. This increase may reflect a positive feed-back mechanism, further enhancing the modulatory effects of CCK-8 on dopamine neurotransmission.

Adult↗
PubMed1992

Ganglioside GM1 counteracts the enhancing effects of subacute toluene exposure on apomorphine-induced locomotor activity.

Previous studies indicate that subacute toluene exposure enhances the effects of postsynaptic doses of apomorphine on locomotor activity in the rat. We have now studied the effects of the ganglioside GM1 on toluene-affected apomorphine-induced (1 mg/kg, s.c.) locomotion, motility, and rearing. Treatment with GM1 (10 mg/kg, i.p., 1 h before exposure) was found to counteract or even reverse the enhancing effect of toluene on apomorphine-induced locomotion and rearing, but had similarly to toluene no significant effects on apomorphine-induced motility or on spontaneous locomotor activity. The antagonistic effects of GM1 may be due to its ability to block toluene-induced changes in D2 receptor binding.

Animals↗
PubMed1992

Chronic nicotine treatment decreases dopamine D2 agonist binding in the rat basal ganglia.

To elucidate possible actions of nicotine on dopamine D2 receptor binding, the effect of chronic continuous (-)nicotine treatment (osmotic pumps s.c., 0.125 mg kg h-2, 14 days) was studied in the binding of [3H]N-propylnorapomorphine ([3H]NPA) and [125I]sulpride in coronal cryostat sections in the rat. Quantitative autoradiography showed that nicotine decreased the binding of [3H]NPA in the basal ganglia, preferentially in the nucleus accumbens and olfactory tubercle. In contrast, [125I]sulpride binding was not affected. Nicotine decreased the KD value of [3H]NPA by 27% and decreased the Bmax value by 17%, using filter-wiped sections. These results indicate that chronic continuous nicotine treatment affects the D2 receptor and that this effect may be involved in the development of nicotine dependence.

Animals↗
PubMed1991

Biochemical characterization of the intramembrane interaction between neurotensin and dopamine D2 receptors in the rat brain.

In order to better understand the neuroleptic-like effects of neurotensin in vivo, the effects of neurotensin in vitro on dopamine D2 and D1 agonist and antagonist binding sites were characterized in membranes from the neostriatum and the subcortical limbic area. Neurotensin increased the KD but not the Bmax value of S(-)[N-propyl-3H(N)]propylnorapomorphine [( 3H]NPA) binding sites with a maximal increase of 20-40% at 3-10 nM of neurotensin in both areas. The KD increase was preferentially due to an increase in the dissociation rate. The maximal reduction of [3H]NPA binding (35%) was obtained within 5 min from the addition of neurotensin. Neurotensin increased the KH of dopamine vs [3H]raclopride binding and, in the presence of GTP, also KL. Neurotensin did not affect the percentage of binding sites in the high vs low affinity states or the binding characteristics of [3H]spiperone, [3H]SKF 38393, and [3H]SCH 23390. Serotonin (10 nM), neuropeptide Y (10 nM), Substance P (10 nM), dynorphin A (10 nM), morphine (10 nM), nicotine (100 nM), gamma-amino-n-butyric acid (1 microM), or N-methyl-D-aspartate (1 microM) did not affect [3H]NPA binding. These results indicate that neurotensin in vitro selectively reduces D2 agonist affinity by an enhancement of the dissociation rate. This antagonistic intramembrane interaction may underlie the neuroleptic-like effects of neurotensin at low concentrations in vivo on D2 agonist binding, dopamine release, and on D2-mediated behaviours.

Animals↗
PubMed1991

Activation of 5-hydroxytryptamine1A receptors increases the affinity of galanin receptors in di- and telencephalic areas of the rat.

Since galanin in vitro selectively increases the KD value of 5-HT1A receptors without altering the binding of 5-HT1B or 5-HT2 receptors, we have studied whether 5-HT1A receptor activation in turn may affect galanin binding in the ventral di- and telencephalon and the substantia nigra of the rat. As analyzed by autoradiography, the binding of 125I-galanin was increased by about 55% in the presence of 3-30 nM of 8-OH-2-(di-n-propylamino)-tetralin (DPAT) in the paraventricular thalamic nucleus, the nucleus reuniens and rhomboideus, the zona incerta, the medial and the lateral hypothalamus, and the medial and the lateral amygdaloid area, but not in the pars compacta of the substantia nigra, which lacks 5-HT1A binding sites. DPAT (10 nM) reduced the IC50 values of galanin at 125I-galanin binding sites by approximately 55% within all the analyzed di- and telencephalic regions. The overall increase in BO values was 50 +/- 11%. Using the filter wipe technique in cryostat sections at Bregma -2.8 mm covering all the brain regions at this level, DPAT (10 nM) decreased the IC50 values of galanin from 21.6 +/- 1.1 nM (control) to 15.5 +/- 0.9 nM, and increased the BO values by 19.4 +/- 4.1%. In membrane preparations from the ventral di- and telencephalon, DPAT decreased the IC50 values of galanin binding sites by 20 +/- 3% at 100 nM of DPAT. This effect could be completely blocked by the specific 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗