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G von Euler

Publications and source records attributed to G von Euler.

At least 55 records · Page 3Linked to original sources
PubMed1991

Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes.

Since high-affinity adenosine A2 receptors (A2a) are localized exclusively in dopamine-rich regions in the central nervous system and mediate inhibition of locomotor activity, we have examined the effect of A2a receptor activation on D1 and D2 receptor binding in membrane preparations of the rat striatum. The A2a agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'- N-ethylcarboxamidoadenosine (CGS 21680) increased the Kd of the dopamine D2 agonist L-(-)-N-[3H]propylnorapomorphine without affecting the Bmax. The increase in Kd was maximal (40%) at 30 nM CGS 21680. CGS 21680 (30 nM) decreased the dopamine-induced inhibition of [3H]raclopride (a D2 antagonist) binding due to an increase (about 3-fold) in KH and KL, the dissociation constants of high- and low-affinity binding sites. The effects of CGS 21680 were antagonized by the adenosine antagonist 8-phenyltheophylline (10 microM). (-)-N6-(2-Phenylisopropyl)adenosine produced an effect similar to that of CGS 21680, provided the concentration used was high enough to stimulate A2a receptors (300 nM). GTP (50 microM) also decreased the dopamine-induced inhibition of [3H]raclopride binding but, in contrast to CGS 21680, GTP decreased the proportion of D2 receptors in the high-affinity state. CGS 21680 (30 nM) did not affect the Kd or Bmax of [3H]raclopride and failed to affect ligand binding to D1 receptors. Thus, stimulation of A2a receptors potently reduces the affinity of D2 agonist binding sites within the plasma membrane of striatal neurons. This A2a-D2 interaction may underlie the neuroleptic-like actions of adenosine agonists and the enhancing effects of adenosine antagonists, such as caffeine, on locomotor activity.

Adenosine↗
PubMed1991

Subacute exposure to low concentrations of toluene affects dopamine-mediated locomotor activity in the rat.

The effects of low concentrations of toluene (40-80 ppm, 3 days, 6 h/day) were investigated on spontaneous and on apomorphine-induced locomotor activity in the rat, and were correlated to effects on S(-)[N-propyl-3H(N)]-propylnorapomorphine ([3H]NPA) binding in rat neostriatal membranes, on membrane fluidity, membrane leakage, and calcium levels in synaptosomes from the frontoparietal cortex, the neostriatum and the subcortical limbic area, and on serum hormone levels. Toluene exposure (80 ppm, post-exposure delay 18 h) alone did not affect locomotor activity, but attenuated apomorphine-induced (0.05 mg/kg, s.c.) suppression of rearing, and potentiated apomorphine-induced (1 mg/kg, s.c.) increases in locomotion and rearing. Toluene exposure increased the KD value of [3H]NPA binding without affecting the Bmax. All these effects were absent at 40 ppm of toluene or at a post-exposure delay of 42 h. Toluene exposure (80 ppm, post-exposure delay of 18 h) did not affect the serum levels of prolactin, TSH, corticosterone, or aldosterone, or synaptosomal membrane fluidity and calcium levels, whereas membrane leakage was increased in the neostriatum. The present study indicates that the reduction of D-2 receptor affinity by short-term, low-dose toluene exposure is accompanied by a reduced D-2 autoreceptor function and an enhanced postsynaptic D-2 receptor function.

Administration, Inhalation↗
PubMed1991

Dopamine D2 receptors attenuate phosphatidylinositol 4,5-bisphosphate in synaptosomal membranes from rat neostriatum.

The effects of dopamine on [32P]ATP-labelled phosphatidylinositol 4-phosphate, phosphatidylinositol 4,5-bisphosphate, and phosphatidic acid were analyzed by TLC in synaptosomal membranes of the rat neostriatum. The incorporation of 32P into these compounds was found to be stable within 1 min and was maintained during the 30 min of incubation. Dopamine (0.1-10 microM) was found to attenuate the levels of phosphatidylinositol 4,5-bisphosphate without affecting the levels of phosphatidylinositol 4-phosphate or phosphatidic acid. The maximal decrease (-35 +/- 4%) was reached at 10 microM of dopamine after 30 min of incubation. The dopamine (0.1 microM)-induced decrease was blocked by the D2 selective antagonist raclopride (1 microM), but not by the D1 selective antagonist SCH 23390 (1 microM). These findings indicate the existence of an intramembrane coupling of dopamine D2 receptors to phosphoinositide turnover and may underlie some of the physiological effects of D2 receptor stimulation.

Adenosine Triphosphate↗
PubMed1991

Neurotensin decreases the affinity of dopamine D2 agonist binding by a G protein-independent mechanism.

To examine whether GTP-binding proteins (G proteins) mediate the ability of neurotensin to lower the affinity of dopamine D2 agonist binding, the modulation by neurotensin in vitro of N-[3H]propylnorapomorphine [( 3H]-NPA) binding was investigated following pretreatment with pertussis toxin and N-ethylmaleimide in rat neostriatal membranes. Preincubation with N-ethylmaleimide (100 microM) markedly inhibited pertussis toxin-induced back-ADP ribosylation of three proteins with apparent molecular masses of 41, 40, and 39 kDa, respectively. This inhibition was prevented by adding dithiothreitol (250 microM) during the preincubation. N-Ethylmaleimide increased the KD (180 +/- 30%) and decreased the Bmax (-31 +/- 9%) of [3H]NPA binding sites but did not affect the binding properties of the selective D2 antagonist [3H]raclopride. N-Ethylmaleimide pretreatment did not affect the neurotensin (3 nM)-induced increase in the KD of [3H]NPA binding sites. Pertussin toxin treatment in vivo and in vitro was similarly ineffective. In conclusion, the present study indicates that neurotensin modulation of D2 agonist binding in neostriatal membranes is not mediated by G proteins.

Adenosine Diphosphate Ribose↗
PubMed1990

Intraventricular injection of neurotensin reduces dopamine D2 agonist binding in rat forebrain and intermediate lobe of the pituitary gland. Relationship to serum hormone levels and nerve terminal coexistence.

In order to investigate neurotensin-dopamine receptor interactions in vivo, the effects of intraventricular injection of neurotensin were analyzed on S(-)[N-propyl-3H(N)]propylnorapomorphine [( 3H]NPA) binding in cryostat sections of the forebrain, hypothalamus and pituitary gland, and on serum levels of prolactin, luteinizing hormone and corticosterone in the male rat. The relationship of modulation of [3H]NPA binding with neurotensin-dopamine coexistence in nerve terminals was analyzed by investigating coexistence of neurotensin and tyrosine hydroxylase (TH) immunoreactive nerve terminals in various brain areas, using a double immunohistofluorescence procedure. Intraventricular injections of neurotensin (0.03-3 nmol, 30 min) reduced dose-dependently specific [3H]NPA binding (0.25 nM) in the caudate-putamen (-38 +/- 4%), nucleus accumbens (-42 +/- 5%), tuberculum olfactorium (-52 +/- 7%) and in the intermediate lobe of the pituitary gland (-17 +/- 2%). Coexistence of neurotensin and TH was demonstrated in nerve terminals in the prefrontal, cingulate, piriform and entorhinal cortex and in the cortical and deep nuclei of the amygdaloid cortex. It was not possible to demonstrate coexistence in the caudate-putamen, nucleus accumbens, tuberculum olfactorium and median eminence, in view of the high density of dopamine nerve terminals present in relation to the few visualized neurotensin terminals. Nor could coexistence be demonstrated in the few remaining TH-positive nerve terminals following unilateral 6-hydroxydopamine lesions (8 micrograms per 4 microliters; one week) in spite of increased numbers of neurotensin-containing cell bodies and terminals in the ipsilateral dorsomedial caudate. Neurotensin injection markedly decreased serum prolactin levels and increased serum corticosterone levels by about 60%, whereas serum levels of luteinizing hormone were unaffected. The present study indicates that central dopamine D2 receptors may be regulated by neurotensin in vivo and that the neurotensin involved most likely is released from nerve terminals not containing dopamine, since fibers showing coexistence were only found in prefrontal and limbic cortical areas.

Animals↗
PubMed1990

Centrally injected neuropeptide Y (13-36) produces vasopressor effects and antagonizes the vasodepressor action of neuropeptide Y (1-36) in the awake male rat.

Intraventricular injections of the Y2 neuropeptide Y (NPY) receptor agonist porcine NPY (13-36) (pNPY (13-36); 25-3000 pmol) produced a dose-dependent increase (up to 14%; ED50 value of 0.3 nmol for overall effects and 0.97 nmol for the peak effects) in mean arterial blood pressure in the awake, unrestrained male rat without affecting heart rate. Furthermore, a subthreshold dose of pNPY (13-36) (25 pmol) counteracted the vasodepressor action of the parent compound pNPY (1-36) (75 pmol), which also acts at NPY receptors of the Y1 type. These results suggest that NPY receptors of the Y1 and Y2 type have opposing actions in central cardiovascular regulation.

Animals↗
PubMed1990

Acute and subchronic corticosterone treatment differentially modulates subcortical limbic and neostriatal nicotinic cholinergic receptors.

The effects of acute and subchronic corticosterone treatment were analyzed on the competition by (-)nicotine ((-)nicotine hydrogen(+)-tartrate) on N-[3H]methylcarbamyl choline iodide ([ 3H]MCC) binding sites in membranes from the subcortical limbic forebrain and the neostriatum. Acute treatment with corticosterone (5 mg/kg, i.p., 2 h) increased the IC50 values of (-)nicotine by 230% in the subcortical limbic areas but not in the neostriatum. Subchronic corticosterone treatment (5 mg/kg, twice a day, 7 days) increased the IC50 values of (-)nicotine by 50% and slightly decreased the specific binding of [3H]MCC (5 nM) in the subcortical limbic area. In the neostriatum, subchronic treatment with corticosterone instead decreased by 50% the IC50 values of (-)nicotine and slightly increased the specific binding of [3H]MCC. The results indicate that corticosterone treatment selectively reduces the affinity of nicotinic cholinergic receptors within the subcortical limbic forebrain.

Animals↗
PubMed1990

Neurotensin reduces the affinity of dopamine D2 receptors in membranes from post mortem human caudate-putamen.

The effects of neurotensin in vitro were investigated on the binding characteristics of N-[3H]propylnorapomorphine [( 3H]NPA) binding sites in crude membrane preparations from post mortem human caudate-putamen, obtained within 10 h after death from 3 patients without reported neurological or psychiatric diseases. Neurotensin (0.1-30 nM) was found to increase the KD value of [3H]NPA binding sites with a maximal increase of about 50% (420 +/- 45 pM) at 3 nM of neurotensin, without significantly affecting the Bmax value (123 +/- 20 pmol/g protein). These results indicate the existence of an intramembrane regulation by neurotensin receptors of D2 receptors in the human caudate-putamen.

Aged↗
PubMed1990

Ganglioside GM1 prevents and reverses toluene-induced increases in membrane fluidity and calcium levels in rat brain synaptosomes.

The effects of exposure to ganglioside GM1 and to toluene in vitro upon synaptosomal integrity have been examined using fluorescence polarization of two probes: 1-[4(trimethylamino)phenyl]-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH) to measure membrane anisotropy, and the fluorescent indicator fura-2 to assay levels of cytosolic calcium [( Ca2+]i). The anisotropy of both TMA-DPH and DPH was decreased by toluene, implying increased membrane fluidity. The decrease in TMA-DPH but not in DPH anisotropy was prevented by pretreatment with GM1 in concentrations as low as 10 microM. This is not an additive interaction since 10 microM of GM1 alone did not significantly modulate TMA-DPH anisotropy. When the GM1 treatment succeeded the addition of toluene the decrease in anisotropy of both probes was reversed. Toluene treatment increased [Ca2+]i in a dose- and time-dependent manner. This increase could partially be both prevented and reversed by treatment with 50 microM of GM1. These effects may reflect an additive interaction, since this concentration of GM1 alone reduced [Ca2+]i. The present results show that toluene increases membrane fluidity and intracellular calcium levels. These effects may be counteracted by the endogenous compound GM1.

Animals↗
PubMed1990

Regulation of endocrine function by the nicotinic cholinergic receptor.

One important neuroendocrine action of nicotine in the male rat is an increase in the secretion of corticosterone which is seen upon acute and acute intermittent exposure to nicotine. Tolerance develops to this action of nicotine upon chronic exposure, and in the withdrawal phase serum corticosterone levels are substantially reduced. In contrast, no significant increases of serum corticosterone levels were observed upon acute intermittent treatment with nicotine in the dioestrous rat. Available evidence indicates that corticosterone can modulate dopamine transmission in the basal ganglia via glucocorticoid receptors within the nucleus accumbens and neostriatum, and via glucocorticoid receptor immunoreactivity in nigrostriatal and mesolimbic dopamine pathways. Through concerted pre- and postsynaptic actions glucocorticoids may decrease dopamine transmission, especially that mediated by D2 receptors in these regions. In view of the hypothesis that the mesolimbic dopamine pathways mediate the euphoric effects of nicotine, the secretion of corticosterone induced by nicotine in the smoking male may substantially influence the mood elevating activity of nicotine. Thus, individual smoking habits may depend on the ability of nicotine to induce corticosterone secretion, which obviously would also vary with the degree of stress. The glucocorticoids may in a similar way influence the arousal action of nicotine because of the high number of glucocorticoid receptors present both in noradrenaline cell bodies of the locus ceruleus and within the entire cerebral cortex.

Animals↗
PubMed1990

Involvement of cholecystokinin receptors in the control of striatal dopamine autoreceptors.

The interaction of locally perfused cholecystokinin-8 (sulphated) with systemically administered apomorphine was studied on the release of dopamine and its metabolites using microdialysis in the neostriatum of the halothane-anaesthetized male rat. Dialysate levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were assayed by high performance liquid chromatography in combination with electrochemical detection. Perfusion with cholecystokinin-8 (100 microM but not 1 microM or 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC or HVA. At low concentrations (1 microM and 10 nM but not 1 nM), cholecystokinin-8 counteracted the inhibitory effect of apomorphine (0.05 mg/kg, s.c.) on dopamine release. This counteraction was antagonized by perfusion with the cholecystokinin-8 antagonist proglumide (3 microM). At this concentration, proglumide perfused alone was without effect on basal or apomorphine-reduced levels of dopamine. The results indicate a facilitatory effect of cholecystokinin-8 on dopamine release in rat neostriatum only at high concentrations. At lower concentrations, cholecystokinin-8 appears to modulate dopamine release by an inhibitory effect on dopamine autoreceptors possibly involving an intramembrane interaction between presynaptic cholecystokinin-8 receptors and dopamine autoreceptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Changes in pituitary-adrenal activity affect the apomorphine- and cholecystokinin-8-induced changes in striatal dopamine release using microdialysis.

The effects of apomorphine (0.05 mg/kg, i.p.) and cholecystokinin-8 (sulphated; CCK-8) were analyzed on the levels of dopamine and its metabolites using intrastriatal microdialysis in the adrenalectomized rat with or without corticosterone replacement treatment (5 mg/kg, twice daily for 7 days, last dose given 2 h before killing). Adrenalectomy did not affect the basal release of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) or homovanillic acid (HVA). However, the apomorphine-induced decrease in dopamine release was attenuated following adrenalectomy. Furthermore, there was an enhancement of the apomorphine-induced decrease in DOPAC levels without any modulation of the apomorphine-induced effects on HVA levels. In contrast, the CCK-8-induced increase in dopamine levels was potentiated following adrenalectomy. This potentiation was fully counteracted by replacement treatment with corticosterone. These results indicate that corticosterone may be involved in the regulation of dopamine release, perhaps through glucocorticoid receptors in nigral dopamine cells controlling inter alia the synthesis of G-proteins involved in the regulation of dopamine autoreceptors and CCK-8 receptors located on dopamine nerve terminals or of the receptor proteins themselves.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Persistent effects of chronic exposure to styrene on the affinity of neostriatal dopamine D-2 receptors.

We have investigated whether chronic exposure to styrene could inflict persistent effects on the binding characteristics of dopamine D-2 agonist binding sites in rat neostriatal membranes. Styrene exposure (1000 ppm, 6 months, 16 h/d overnight, and left without exposure for another 5 months) caused a marked increase (+160%) in the IC50 value of dopamine without significantly affecting the total amount of specifically bound [3H]raclopride. The specific [3H]raclopride binding in membranes from subcortical limbic areas was too low to yield acceptable displacement curves. These data indicate that chronic exposure to styrene can induce a persistent decrease in affinity of the neostriatal dopamine D-2 agonist binding sites, possibly mediated by membrane perturbations.

Animals↗
PubMed1990

On the role of neuropeptide Y in information handling in the central nervous system in normal and physiopathological states. Focus on volume transmission and neuropeptide Y/alpha 2 receptor interactions.

The NPY neurons play an important role in information handling in the CNS by their ability to interact in both wiring and volume transmission at the network, local circuit and synaptic level. The importance of NPY/alpha 2 receptor-receptor interactions in cardiovascular, neuroendocrine and vigilance control is emphasized. Alterations in these receptor-receptor interactions take place in the spontaneously hypertensive rats as well as in the ischemic brain, which may have profound consequences for the information handling and contribute to the functional alterations found in these pathophysiological states. Finally, in the aging brain there appears to exist a marked reduction in NPY transmission line, which may affect higher brain functions, such as learning and memory retrieval. The most impressive result is, however, the indications of a role for NPY in volume transmission, where NPY appears to produce syndromic actions via its conversion into biologically active fragments, which may have preferential actions at Y2 NPY receptors. These syndromic pathways may be altered in the spontaneously hypertensive rat and may be controlled by gonadal steroids and glucocorticoids. Glucocorticoid receptors have been demonstrated in all arcuate NPY neurons and all NA/NPY and A/NPY costoring neurons.

Aging↗
PubMed1989

Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum.

Microdialysis in the neostriatum of the halothane-anesthetized male rats was used to study the effect of neurotensin on the release of dopamine and its metabolites in the absence or presence of systemic apomorphine treatment. Perfusate levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assayed by high-performance liquid chromatography in combination with electrochemical detection. Perfusion with neurotensin (1000 nM but not 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC and HVA. Systemic treatment with apomorphine (0.05 and 0.5 mg/kg, s.c.) reduced the dialysate levels of dopamine, DOPAC and HVA in a dose-related way. Neurotensin (10 nM but not 1 nM) counteracted the inhibitory effect of apomorphine on dialysate levels of dopamine without affecting those of DOPAC and HVA. The results indicate a facilitatory effect of neurotensin on dopamine release in rat neostriatum. It is suggested that activation of neurotensin receptors may cause a reduction in the affinity of dopamine autoreceptors, since the low dose of neurotensin is able to counteract the inhibitory effect of apomorphine on dopamine release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Acute treatment with clozapine blocks D1 dopamine receptor binding in discrete brain areas of the male rat.

The ability of acute treatment with clozapine in vivo to block D1 receptors in the rat telencephalon and midbrain was investigated using the irreversible inactivation of [125I]SCH 23982 binding sites by N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 6 mg/kg, i.p., 24 h). As analyzed by quantitative autoradiography, clozapine (40 mg/kg, i.p., 15 min before EEDQ administration) was found to produce a partial protection of central D1 receptors in all brain areas investigated, including cerebrocortical regions. These data could perhaps explain the failure of clozapine to induce tardive dyskinesia upon chronic treatment.

Animals↗