Bernard J. Van Vliet

University of Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (15)37.91 Total impact

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    ABSTRACT: In the present study we investigated the possible role of changes in the number of membrane-bound G-proteins in the sensitization of dopamine D1 receptor-stimulated adenylyl cyclase, observed in primary cultures of rat striatal neurons chronically exposed to morphine. Whereas exposure of these neurons to 10 microM morphine for 7 days caused a profound increase in cyclic AMP production, induced by the dopamine D1 receptor agonist SKF 38393 (1 microM), Scatchard analysis of [125I]SCH 23982 binding to membrane preparations revealed that neither the Bmax nor the Kd values of dopamine D1 receptor binding sites were affected. Interestingly, immunoblotting experiments revealed an increase (of more than 50%) in the number of stimulatory G-proteins (G alpha s) in neurons displaying an enhanced adenylyl cyclase activity. In morphine-treated neurons, the number of inhibitory G-proteins (G alpha i) appeared to be slightly reduced (by about 16%). Moreover, the observation that cholera toxin (0.1 nM)-stimulated cyclic AMP production, unlike that induced by forskolin (1 microM), was enhanced in morphine-treated neurons, indicates a causal relationship between the reciprocal changes in G-protein number and the increase of dopamine D1 receptor-stimulated adenylyl cyclase activity. The possible role of these changes in G-protein number in the development of morphine tolerance and dependence is discussed.
    No preview · Article · Apr 1993 · European Journal of Pharmacology

  • No preview · Article · Jun 1992 · Biochemical Society Transactions
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    Preview · Article · May 1992 · Biochemical Society Transactions
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    ABSTRACT: In cultured rat striatal neurons exposed to 10 microM morphine or oxotremorine for 24 hours, we observed an increased (about 30%) dopamine D1 receptor-stimulated cyclic AMP production, whereas no desensitization of mu-opioid receptor or muscarinic cholinergic receptor was found. However, whereas upregulation of dopamine D1 receptor-stimulated adenylate cyclase activity upon 7 days morphine exposure was at least as pronounced as observed after 24 hours of exposure to the opioid, this adaptive phenomenon was virtually absent following one week of oxotremorine treatment. This reduced adenylate cyclase sensitization upon 7 days oxotremorine exposure appeared to coincide with desensitization of muscarinic cholinergic receptors. A possible role of the resistance of mu receptors to desensitization and the (resulting) upregulation of the neuronal adenylate cyclase system upon chronic receptor activation in the development of opiate tolerance and dependence is suggested.
    No preview · Article · Feb 1992 · Life Sciences
  • Bernard J. Van Vliet · George Wardeh · Arie H. Mulder · Anton N.M. Schoffelmeer

    No preview · Article · Jan 1992 · European Journal of Pharmacology
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    ABSTRACT: Rat striatal neurons cultured in serum-free, hormone-supplemented medium, were exposed to 10 microM morphine for several hours or days before intracellular cyclic AMP production was measured. Dopamine D1 receptor- and beta-adrenoceptor-stimulated cyclic AMP production were profoundly increased upon morphine exposure (up to 150% of control). In contrast, cyclic AMP production induced by direct activation of the catalytic unit of adenylate cyclase with forskolin remained unaffected. Interestingly, the relative inhibitory effect of the mu-opioid receptor agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) on dopamine D1 receptor-stimulated cyclic AMP production was unchanged after exposure to morphine. On the other hand, unlike mu-opioid receptors chronically exposed to morphine, beta-adrenoceptors mediating activation of adenylate cyclase were rapidly desensitized upon prolonged exposure of the neurons to isoprenaline. It is suggested that tolerance to morphine may be caused by the fact that morphine is acting against up-regulated signal transduction mechanisms rather than by mu receptor desensitization. Moreover, this enhanced effector system function may be involved in opioid dependence. The adaptive changes following morphine treatment appear to be independent of possible alterations at the level of dopaminergic or noradrenergic nerve terminals which are not present in primary cultures of rat striatum.
    No preview · Article · Nov 1991 · European Journal of Pharmacology
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    ABSTRACT: Timed-pregnant rats received a semisynthetic diet with or without morphine (0.5-1 mg/g) for 2 weeks. After 21 days of gestation the morphine-dependent dams were decapitated and the foetal brains were dissected. Chronic morphine administration caused a profound increase of adenylate cyclase activity stimulated by postsynaptic D1 dopamine receptors in striatal slices. The relative inhibitory effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) on D1-stimulated cyclic AMP (cAMP) production was unaffected. In contrast, cAMP production induced via direct activation of the catalytic unit of adenylate cyclase with forskolin was not changed upon long-term morphine treatment, although DAGO strongly inhibited the effect of forskolin. The electrically evoked release of [3H]noradrenaline (NA) from superfused neocortical slices was strongly enhanced upon morphine treatment, whereas release induced by the calcium ionophore A23187, bypassing voltage-sensitive calcium channels, was unchanged. Again, the inhibitory effect of the mu receptor agonist DAGO was unaffected in neocortical slices from morphine-treated rats. It is suggested that tolerance to morphine may be caused by the fact that the opiate is acting against up-regulated signal transduction mechanisms, rather than by desensitization of central mu-opioid receptors. The pre- and postsynaptic changes may include an enhanced expression and/or biochemical modification of D1 receptors, Gs proteins and calcium channels in central neurons on which mu-opioid receptors are present. At the same time, these adaptive changes may underlie morphine withdrawal phenomena.
    No preview · Article · Nov 1991 · European Journal of Pharmacology
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    ABSTRACT: The beta-adrenoceptor-sensitive adenylate cyclase in primary cultures of rat striatal neurons was inhibited by opioids, unlike that in rat striatal slices. Isoprenaline (1 microM)-stimulated cyclic AMP production was dose dependently inhibited by the mu-opioid receptor agonist. [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, EC50 = 0.02 microM, 36% inhibition), and only slightly reduced by relatively high concentrations of the delta-opioid receptor agonist, [D-penicillamine2, D-penicillamine5]enkephalin (DPDPE, 1 microM). The highly selective and potent delta-opioid receptor agonist. [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), and the kappa-opioid receptor agonist, U50-488, were ineffective in concentrations up to 3 microM. Naloxone reversed equally well the inhibitory effects of DPDPE and of DAGO, indicating the involvement of functional mu-opioid receptors. The isoprenaline (1 microM)-stimulated adenylate cyclase activity in cultured glial cells, which exceeded that in neurons about 10-fold, was not affected by opioids. Therefore, opioids were ineffective in rat brain slices probably due to the fact that cyclic AMP production induced by beta-adrenoceptor activation occurs primarily in the glial cells, where it is not subject to inhibition by opioids. These data indicate for the first time the existence of an interaction between functional mu-opioid receptors and beta-adrenoceptors on striatal neurons of the rat.
    No preview · Article · Apr 1991 · European Journal of Pharmacology
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    ABSTRACT: The receptors mediating the inhibition of D1 dopamine receptor-stimulated adenylate cyclase by opioids were examined in primary cultures of rat neostriatal neurons. Adenylate cyclase activity was dose-dependently increased by the selective D1 dopamine receptor agonist SKF 38393 (EC50 = 0.05 microM). This stimulation was fully antagonized by the selective D1 dopamine receptor antagonist SCH 23390 (1 microM). SKF 38393 (1 microM)-stimulated adenylate cyclase activity was strongly reduced (by almost 60%) by the highly selective mu-agonist [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO; EC50 = 0.006 microM) and high concentrations of the selective delta-agonist [D-Ser2(O-tert-butyl), Leu5]-enkephalyl-Thr6 (DSTBU-LET; EC50 = 0.13 microM) but not by the selective delta-agonist [D-penicillamine2, D-penicillamine5]enkephalin (DPDPE). D1 dopamine receptor-stimulated adenylate cyclase activity was also slightly reduced (by approximately 20%) by high concentrations of the kappa-agonist U50,488 (EC50 = 0.63 microM). The inhibitory effects of submaximally effective concentrations of DAGO, DSTBULET, and U50,488 were equally well antagonized by the mu-opioid receptor-selective antagonist naloxone (EC50 of approximately 0.1 microM). Neither the irreversible delta-ligand fentanyl isothiocyanate (1 microM) nor the reversible delta-antagonist ICI 174864 (1 microM) reversed the inhibitory effects of DSTBULET. The inhibitory effects of DAGO and U50,488 were equally well reversed by high concentrations (greater than 0.1 microM) of the kappa-opioid receptor-selective antagonist norbinaltorphimine. The effect of DAGO (1 microM) was already detectable after 1 day in culture, whereas DPDPE (1 microM) had no effect even after 28 days in culture. These data indicate that an homogeneous population of mu-opioid receptors coupled as inhibitors to D1 dopamine receptor-stimulated adenylate cyclase is expressed in rat neostriatal neurons in primary culture.
    No preview · Article · Nov 1990 · Journal of Neurochemistry
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    ABSTRACT: Based on the results of in vivo studies, the thiazoloazepine derivative B-HT 920 has been proposed to be a selective agonist of dopamine autoreceptors. In the present study, we investigated the effects of B-HT 920 in two functional in vitro model systems of D2 receptors and compared these effects with the effects of the classical D2 agonist LY 171555. B-HT 920 and LY 171555 concentration dependently inhibited the electrically evoked release of radiolabeled dopamine and acetylcholine and the forskolin-induced stimulation of adenylate cyclase activity in rat striatal tissue slices with comparable efficacies. In striatal tissue slices prepared after 6-hydroxydopamine-induced destruction of dopaminergic terminals, both drugs were still able to inhibit forskolin-stimulated adenylate cyclase activity with a efficacy similar to that in tissue obtained from unlesioned rats. It is concluded that, in vitro, B-HT 920 is an agonist at both presynaptic and 'normosensitive' postsynaptic D2 receptors showing relatively high intrinsic activity.
    No preview · Article · Nov 1990 · European Journal of Pharmacology
  • B J van Vliet · A.H. Mulder · A.N.M. Schoffelmeer

    No preview · Article · Feb 1990 · Progress in clinical and biological research
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    ABSTRACT: Endogenous amino acid release was measured in developing cerebellar neuronal cells in primary culture. In the presence of 25 mM K+ added to the culture medium, cerebellar cells survived more than 3 weeks and showed a high level of differentiation. These cultures are highly enriched in neurons, and electron-microscopic observation of these cells after 12 days in vitro (DIV) confirmed the presence of a very large proportion of cells with the morphological characteristics of granule cells, making synapses containing many synaptic vesicles. Synaptogenesis was also confirmed by immunostaining the cells with antisera against synapsin I and synaptophysin, two proteins associated with synaptic vesicles. From these cultures, endogenous glutamate release stimulated by 56 mM K+ was already detected after only a few days in culture, the maximal release value (1,579% increase over basal release) being reached after 10 DIV. In addition to that of glutamate, the release of aspartate, asparagine, alanine, and, particularly, γ-aminobutyric acid (GABA) was stimulated by 56 mM K+ after 14 DIV, but to a lesser extent. No increase in serine, glutamate, taurine, or tyrosine release was observed during K+ depolarization. The effect of K+ on amino acid release was strictly Ca2+-dependent. Stimulation of the cells with veratridine resulted in a qualitatively similar effect on endogenous amino acid release. In the absence of Ca2+, 30% of the veratridine effect persisted. The Ca2+-dependent release was quantitatively similar after stimulation by veratridine and K+. Treatment of cerebellar cells with tetanus toxin (5 μg/ml) for 24 h resulted in a total inhibition of the Ca2+-dependent component of the glutamate release evoked by K+ or veratridine. It is concluded that glutamate is the main amino acid neurotransmitter of cerebellar cells developed in primary culture under the present conditions and that glutamate is probably mainly released through the exocytosis of synaptic vesicles.
    No preview · Article · May 1989 · Journal of Neurochemistry
  • J P Pin · Bernard J. Van Vliet · J Bockaert
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    ABSTRACT: The effects of non-NMDA receptor agonists were tested on endogenous GABA and [3H]GABA release from highly purified striatal neurons differentiated in primary culture. Kainate (KA), glutamate (Glu) and quisqualate (QA) stimulated [3H]GABA release with EC50S = 85 +/- 20 (n = 6), 6.21 +/- 1.42 (n = 3) and 0.135 +/- 0.035 (n = 3) microM, respectively. KA was the most potent (in term of efficacy) agonist (maximal response at 10 mM: 935 +/- 51% (n = 6) increase over basal release) followed by Glu (at 100 microM: 404 +/- 34% (n = 5) increase) and QA (at 10 microM: 91 +/- 6% (n = 6) increase). Phencyclidine (PCP), which was without effect on QA- and KA-evoked GABA release, inhibited the Glu response by about 50%. QA totally inhibited KA (50 microM)-evoked GABA release with an IC50 = 0.39 +/- 0.11 (n = 4) in a competitive manner (Ki = 0.39 +/- 0.07 microM (n = 3]. Competitive inhibition of the KA response was also observed with the other agonists of the quisqualate receptor, Glu and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), suggesting that Glu, QA and AMPA act as partial agonists at the KA receptor. gamma-D-Glutamylaminomethylsulfonic acid (GAMS) also inhibited (IC50 = 2.1 mM) the KA response competitively. However the inhibition by GAMS and QA was not additive. The response to QA was rapidly inactivated (no response after 3 min stimulation) in contrast to the KA-evoked GABA release which remained maximal for at least 3 min. When neurons were first exposed to concanavalin A (con A), a lectin known to inhibit Glu receptor desensitisation on insect muscles, the QA response remained maximal for at least 6 min. Con A greatly enhanced the maximal responses to QA and AMPA and decreased their apparent affinities. The KA-evoked GABA release (but not the veratridine and NMDA effects) was also augmented (no change in the EC50 value) by con A. It is proposed that QA, AMPA and KA act at the same receptor-channel complex (termed G2 receptor) which is desensitised more rapidly when stimulated by QA or AMPA than when stimulated by KA.
    No preview · Article · Apr 1989 · European Journal of Pharmacology

  • No preview · Article · Feb 1989 · Pharmaceutisch weekblad
  • Anton N.M. Schoffelmeer · Bernard J. Van Vliet · George Wardeh · Arie H. Mulder
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    ABSTRACT: The [3H]dopamine release induced from superfused rat neostriatal slices by 15 mM K+ was enhanced and that of [14C]acetylcholine was inhibited by oxotremorine in a concentration-dependent manner with a similar EC50 value (0.1 microM). Pirenzepine antagonized the modulatory effects of 1 microM oxotremorine on the release of both neurotransmitters with the same EC50 value (0.3 microM), whereas gallamine up to a concentration of 30 microM antagonized the inhibitory effect of oxotremorine on [14C]acetylcholine release only (EC50: 3 microM). These data strongly suggest that, although these functionally different populations of muscarine receptors cannot be regarded as being pharmacologically different (i.e. as M-1 and M-2 receptors, respectively), autoreceptors may still be selectively modified by drugs such as gallamine possibly acting on binding sites adjacent to the conventional muscarine receptor recognition site.
    No preview · Article · Oct 1986 · European Journal of Pharmacology