F Hogenboom

VU University Amsterdam, Amsterdam, North Holland, Netherlands

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Publications (43)182.44 Total impact

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    ABSTRACT: The modulation of the electrically evoked release of [3H]dopamine (DA) and [3H]noradrenaline (NA) by opioid receptor activation was examined in superfused slices of rat mediobasal hypothalamus (MBH). [3H]DA release was inhibited (maximally by 30-35%) by both the selective kappa-agonist U 50,488 (1 nM to 1 microM) and the selective mu-agonist DAGO (0.01-1 microM) but not by the delta-selective agonist DPDPE (1 microM). Naloxone partly antagonized the inhibitory effect of U 50,488 and completely that of DAGO, whereas the selective kappa-antagonist norbinaltorphimine (nor-BNI) only antagonized the inhibition caused by U 50,488. The dopamine D2 receptor agonist quinpirole as well as the alpha 2-adrenoceptor agonist oxymetazoline both decreased (by 25-30%) the evoked overflow of [3H]DA. The evoked release of [3H]NA was not modulated by any of the opioid agonists nor by quinpirole. However, the alpha 2-adrenoceptor agonist oxymetazoline inhibited the release of [3H]NA by 30-40%. Activation of alpha 2-adrenoceptors by oxymetazoline prevented the inhibitory effect of U 50,488, but not DAGO, on evoked [3H]DA release, whereas the selective kappa-antagonist nor-BNI antagonized the inhibition by oxymetazoline of [3H]DA, but not [3H]NA, release. In conclusion, activation of both kappa- and mu-opioid receptors results in an inhibition of evoked DA release from MBH slices but does not modulate NA release. Therefore, several of the reported effects of opioids on hormone secretion may be an (indirect) consequence of a reduction of DA release.(ABSTRACT TRUNCATED AT 250 WORDS)
    Neuroendocrinology 09/1991; 54(2):118-26. · 3.54 Impact Factor
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    ABSTRACT: In the presence of physiological cations (in Krebs-4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid buffer) at 37 degrees C the Ki value's of beta-endorphin for mu- and delta-opioid receptor binding sites in rat neocortical membranes, labeled with [3H][D-Ala2,MePhe4,Gly- ol5]enkephalin (DAMGO) and [3H][D-Ala2-D-Leu5]enkephalin (in the presence of unlabeled DAMGO), respectively, amounted to about 9 and 22 nM. Surprisingly, a very different selectivity pattern for the endogenous opioid peptide was found when the affinity of beta-endorphin for functional presynaptic opioid receptors was examined. Thus, beta-endorphin strongly inhibited the electrically evoked release of [3H]NE from rat neocortical slices with an IC50 value of about 0.5 nM, whereas [14C] acetylcholine release from neostriatal slices was inhibited with an IC50 value of about 100 nM. On the other hand, the electrically evoked release of [3H]dopamine from striatal slices was not affected by beta-endorphin. The inhibitory effects of DAMGO and beta-endorphin on [3H]NE release from neocortical slices were equally well antagonized by naloxone. Moreover, 10 nM of the highly selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen- Thr-NH2 antagonized competitively the inhibitory effect of beta-endorphin on [3H]NE release.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Pharmacology and Experimental Therapeutics 08/1991; 258(1):237-42. · 3.89 Impact Factor
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    ABSTRACT: 1. The potency, relative efficacy and selectivity of a series of kappa-opioid receptor agonists at the mu-, delta- and kappa-opioid receptors mediating inhibition of electrically-induced (radiolabelled) neurotransmitter release from superfused rat brain slices was determined. 2. With regard to their potencies at kappa-receptors mediating inhibition of striatal [3H]-dopamine release, the highest pD2 value (8.7) was found for bremazocine and the lowest (7.1) for U50488; the pD2 values for ethylketocyclazocine (EKC), tifluadom, U69593 and PD117302 were between 8.0 and 8.3. There were no marked differences between the relative efficacies of the kappa-agonists (maximum inhibition being 60-70%). In contrast to the other kappa-agonists, at a concentration of 1 microM, PD117302 caused a significant (25-40%) increase of the spontaneous efflux of tritium. 3. None of the kappa-agonists significantly affected striatal [14C]-acetylcholine (ACh) release, with the exception of a slight inhibitory effect of EKC. The delta-receptor-mediated inhibitory effect of [D-Ala2, D-Leu5]enkephalin (DADLE) on [14C]-ACh release was antagonized in a concentration-dependent manner by bremazocine (0.1 and 1.0 microM) and also partially by EKC (1 microM), but not by the other kappa-agonists. The pA2 value for bremazocine as an antagonist at the delta-receptors involved was 8.0, compared to 7.6 for naloxone. 4. None of the kappa-agonists significantly affected cortical [3H]-noradrenaline (NA) release, with the notable exception of tifluadom, which strongly inhibited release by activating mu-receptors. The mu-receptor-mediated inhibitory effect of Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAMGO) on [3H]-NA release was antagonized in a concentration-dependent manner by bremazocine and EKC, but not by the other K-agonists. The pA2 value for bremazocine as an antagonist at the mu-receptors involved was 8.2, compared to 8.6 for naloxone. 5. Thus, whereas U69593 and PD1 17302 display high potency and selectivity towards K-opioid receptors, the potent benzomorphan K-agonists bremazocine and EKC also appear to be strong mu-opioid receptor antagonists.
    British Journal of Pharmacology 03/1991; 102(2):518-22. · 5.07 Impact Factor
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    ABSTRACT: The ontogeny was examined of functional opioid receptors mediating presynaptic inhibition of neurotransmitter release and inhibition of dopamine (DA)-sensitive adenylate cyclase in the rat brain, using highly selective agonists for mu-, delta- and kappa-receptors. On gestational day 17 (E17) strong inhibitory effects of the selective mu-agonist DAGO on the electrically evoked release of [3H]noradrenaline from cortical slices and of the selective kappa-agonist U-50,488 on the electrically evoked release of [3H]DA from striatal slices were found. Electrically evoked release of [3H]acetylcholine from striatal slices was not detectable before postnatal day 7 (P7), but on that day it was already strongly inhibited by the selective delta-agonist DPDPE. Although mu- and delta-opioid receptors coupled to DA-sensitive adenylate cyclase in the striatum are likely to be physically associated in an opioid receptor complex in the adult, they were found to develop asynchronously. Whereas selective activation of mu-receptors with DAGO resulted in an inhibition of D1 dopamine receptor-stimulated adenylate cyclase activity on E17, activation of delta-receptors with DPDPE was not effective until P14. This study confirms the early appearance of mu- and kappa-opioid receptors and the relatively late development of delta-opioid receptors in the rat brain. Most importantly, it shows that in an early stage of development opioids are already able to mediate modulation of noradrenergic (via activation of mu-receptors) and dopaminergic (via activation of mu- and kappa-receptors) neurotransmission processes. Therefore, these opioid receptor types could play a role in brain development and/or developmental disturbances.
    Developmental Brain Research 07/1990; 54(1):63-9. · 1.78 Impact Factor
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    ABSTRACT: The modulation of the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) by opioid receptor activation was examined in superfused slices from rat nucleus accumbens, olfactory tubercle, and frontal cortex. In all brain areas examined, [3H]DA release was inhibited by the kappa agonist, U 50,488 (1-100 nM), and this inhibition was fully antagonized by the selective kappa antagonist, norbinaltorphimine (nor-BNI). In the frontal cortex, the mu agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 0.01-1 microM), also inhibited the evoked release of tritium. However, further experiments (including the use of the D2-receptor agonist, LY 171555, and the alpha 2-adrenoceptor agonist, oxymetazoline) suggest strongly that in the frontal cortex DAGO only inhibits the release of [3H]catecholamine from noradrenergic nerve terminals, despite the use of desimipramine to prevent the uptake of [3H]DA into these terminals. [14C]ACh release from both the nucleus accumbens and olfactory tubercle, but not from the frontal cortex, was inhibited by DAGO (0.01-1 microM) and the delta agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE, 0.01-1 microM). These inhibitory effects were antagonized by 0.1 microM naloxone but not by 3 nM nor-BNI. The irreversible delta ligand, fentanyl isothiocyanate (FIT, 1 microM), only antagonized the inhibition caused by DPDPE. The results indicate that the inhibitory effects of opioids on the in vitro release of DA from dopaminergic nerve fibres arising from the substantia nigra and the ventral tegmental area are mediated by presynaptic kappa receptors only. In those regions where ACh release is modulated by opioids, the type of opioid receptor involved may depend on the type of neuron, i.e. interneuron or afferent neuron.
    European Journal of Pharmacology 07/1990; 181(3):267-78. · 2.59 Impact Factor
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    ABSTRACT: The ontogeny was examined of functional opioid receptors mediating presynaptic inhibition of neurotransmitter release and inhibition of dopamine (DA)-sensitive adenylate cyclase in the rat brain, using highly selective agonists for μ-, δ- and κ-receptors. On gestational day 17 (E17) strong inhibitory effects of the selective μ-agonist DAGO on the electrically evoked release of noradrenaline from cortical slices and of the selective κ-agonist U-50,488 on the electrically evoked release of DA from striatal slices were found. Electrically evoked release of acetylcholine from striatal slices was not detectable before postnatal day 7 (P7), but on that day it was already strongly inhibited by the selective δ-agonist DPDPE. Although μ- and δ-opioid receptors coupled to DA-sensitive adenylate cyclase in the striatum are likely to be physically associated in an opioid receptor complex in the adult, they were found to develop asynchronously. Whereas selective activation of μ-receptors with DAGO resulted in an inhibition of D1 dopamine receptor-stimulated adenylate cyclase activity on E17, activation of δ-receptors with DPDPE was not effective until P14. This study confirms the early appearance of μ- and κ-opioid receptors and the relatively late development of δ-opioid receptors in the rat brain. Most importantly, it shows that in an early stage of development opioids are already able to mediate modulation of noradrenergic (via activation of μ-receptors) and dopaminergic (via activation of μ- and κ-receptors) neurotransmission processes. Therefore, these opioid receptor types could play a role in brain development and/or developmental disturbances.
    Developmental Brain Research. 01/1990;
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    ABSTRACT: Rat neostriatal slices were superfused with medium containing 0.1 to 30 microM of the dopamine (DA)-releasing agent D-(+)-am-phetamine (AMPH) and the D-2 DA receptor antagonist (-)-sulpiride (10 microM) in the absence or presence of mu-, delta-, and kappa-selective opioids. AMPH dose-dependently enhanced the cyclic AMP production, as measured by its efflux from striatal slices, whereas simultaneous blockade of D-2 DA receptors by (-)-sulpiride strongly potentiated this effect. Both the mu-opioid receptor selective agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (0.01-3 microM) and the delta-opioid receptor selective agonist [D-Phe2-D-Pen5]enkephalin (DPDPE, 0.01-3 microM) inhibited the cyclic AMP efflux, stimulated by 10 microM AMPH in the presence of (-)-sulpiride, by 70 to 80%. The highly selective kappa-opioid receptor agonist U 50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrol-idinyl)- cyclohexyl]benzeneacetamide methanesulfonate hydrate) (0.01-1 microM) had no effect. In contrast, the purported kappa-opioid receptor agonist bremazocine (3-300 nM) inhibited the stimulated adenylate cyclase activity to a similar extent as did [D-Ala2-MePhe4,Gly-ol5]enkephalin and DPDPE. Moreover, the selective irreversible delta-antagonist fentanyl isothiocyanate reversed both the inhibition caused by DPDPE and that caused by bremazocine, whereas the kappa-selective antagonist norbinaltorphimine showed no differences in its potency to antagonize the inhibitory effects of the different opioid agonists. The results indicate that opioids, by activating mu- or delta-, but not kappa-opioid receptors may cause a profound inhibition of adenylate cyclase activity stimulated by activation of (postsynaptic) D-1 DA receptors upon the (presynaptic) release of DA.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Pharmacology and Experimental Therapeutics 07/1989; 249(3):864-8. · 3.89 Impact Factor
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    ABSTRACT: The selectivity of a series of opioid peptides towards the mu-, delta- and kappa-opioid receptors mediating differential inhibition of electrically-induced neurotransmitter release from rat brain slices was studied, viz. cortical [3H]noradrenaline release (inhibited via mu-receptors), striatal [3H]dopamine release (inhibited via kappa-receptors) and striatal [14C] acetylcholine release (inhibited via delta-receptors). The highest affinity pD2 7.4) and selectivity towards mu-receptors was exhibited by Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO), whereas [D-Pen2, D-Pen5]enkephalin (DPDPE) was found to be the most selective delta-receptor agonist (pD2 7.3). Also the hexapeptides [D-Ser2]Leu-enkephalin-Thr (DSLET) and [D-Thr2]Leu-enkephalin-Thr (DTLET) showed a relatively high selectivity and, in addition, a high affinity (pD2 8.2-8.4) for delta-opioid receptors. Both dynorphin(1-13) and dynorphin(1-8) exhibited a high affinity for kappa-receptors (pD2 resp. 8.3 and 8.0), but the latter was far less selective. Both of the dynorphin A-related peptides showed affinity to mu-receptors (pD2 6.7-6.8), but dynorphin(1-8), in contrast to dynorphin(1-13), also displayed a high affinity to delta-receptors (pD2 7.6).
    Neuropeptides 01/1989; 14(2):99-104. · 2.07 Impact Factor
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    ABSTRACT: In Ca2+-free EGTA (1 mmol/l)-containing medium veratrine (3 mumol/l) and ouabain (100 mumol/l) strongly enhanced the efflux of 3H-noradrenaline from superfused rat brain neocortical slices prelabelled with the radioactive amine. In both cases 3H-noradrenaline release was prevented by tetrodotoxin (1 mumol/l). These effects of veratrine and ouabain were virtually additive and independent of whether the noradrenaline uptake carrier was blocked with 1 mumol/l desipramine or not. The adenylate cyclase activator forskolin (10 nmol/l - 10 mumol/l) strongly enhanced veratrine- and ouabain-induced 3H-noradrenaline release, without affecting spontaneous tritium efflux. The release induced by both stimuli was profoundly inhibited by the selective mu-opioid receptor agonist [D-Ala, MePhe4, Gly-ol5]enkaphalin (DAGO, 3 nmol/l - 1 mumol/l) in a concentration-dependent manner. The inhibitory effects of 1 mumol/l DAGO were abolished by 1 mumol/l naloxone. On the other hand, preincubation of the slices for 1 h with the delta-opioid receptor-selective irreversible ligand fentanyl isothiocyanate (1 mumol/l) did not change the inhibitory effects of DAGO. These data show that veratrine- and ouabain-induced 3H-noradrenaline release from central noradrenergic nerve terminals is facilitated by increasing intracellular cyclic AMP levels and reduced by activation of presynaptic mu-opioid receptors, indicating the involvement of exocytotic neurotransmitter release. The results provide further evidence for the hypothesis that under these conditions neurotransmitter release from central noradrenergic neurons is triggerred by a Na+-induced efflux of Ca2+ ions from intracellular stores.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/1988; 338(5):548-52. · 2.15 Impact Factor
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    ABSTRACT: We investigated the effects of [D-Ala2,D-Leu5]enkephalin (DADLE). [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.01-1 microM) and bremazocine (0.001-0.3 microM) on the electrically evoked release of radiolabelled neurotransmitters and on the dopamine (DA)-stimulated cyclic AMP efflux from superfused rat brain slices. The differential inhibitory effects of these agonists on the evoked neurotransmitter release indicate that the opioid receptors mediating presynaptic inhibition of [3H]noradrenaline (NA, cortex), [14C]acetylcholine (ACh, striatum) and [3H]DA (striatum) release represent mu, delta and kappa receptors, respectively. In agreement with this classification, preincubation (60 min) of the slices with the delta-opioid receptor-selective irreversible ligand, fentanyl isothiocyanate (FIT, 0.01-1 microM), antagonized the inhibitory effects of DADLE and DPDPE on striatal [14C]ACh release only. On the other hand, the D-1 DA receptor-stimulated cyclic AMP efflux from striatal slices appeared to be inhibited by activation of mu as well as of delta receptors. In this case, the reversible mu antagonist, naloxone (0.1 microM), fully antagonized the inhibitory effect of the mu agonist, DAGO, without changing the effect of the delta agonist DPDPE but was ineffective as an antagonist in slices pretreated with FIT (1 microM). The inhibitory effect of DAGO on the electrically evoked [3H]NA release was antagonized by naloxone whether the receptors were irreversibly blocked by FIT or not. These data not only further support the existence of independent presynaptic mu-, delta- and kappa-opioid receptors in rat brain but also evidence strongly that mu and delta receptors mediating the inhibition of DA-sensitive adenylate cyclase could share a common binding site (for naloxone and FIT) and, therefore, may represent constituents of a functional opioid receptor complex.
    European Journal of Pharmacology 10/1988; 154(2):169-78. · 2.59 Impact Factor
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    ABSTRACT: The interactions between dopamine and muscarinic receptor subtypes coupled to adenylate cyclase in superfused rat neostriatal slices were investigated using the efflux of cyclic AMP, in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, as a highly sensitive parameter of cyclic AMP production. Cyclic AMP efflux induced by simultaneous activation of (stimulatory) D-1 and (inhibitory) D-2 dopamine receptors by dopamine was reduced profoundly by the muscarinic receptor agonist oxotremorine and by inhibition of acetylcholinesterase with physostigmine, but not by the M-1 muscarinic receptor agonist McN-A-343. In contrast, upon blockade of D-2 receptors with (-)-sulpiride, dopamine-stimulated cyclic AMP efflux was inhibited by oxotremorine and physostigmine as well as by McN-A-343. Cyclic AMP efflux induced by isoprenaline, adenosine or vasoactive intestinal peptide was not affected by oxotremorine. The M-1 receptor-selective antagonist pirenzepine, unlike the nonselective antagonist atropine, was about 10 times less potent in antagonizing the inhibitory effects of (a near-maximally effective concentration of) oxotremorine upon simultaneous D-1 and D-2 receptor activation that upon selective D-1 receptor activation (i.e., upon blockade of D-2 receptors). In the latter case, pirenzepine was about 5 times more effective as an antagonist when muscarinic receptors were activated by McN-A-343 than upon exposure of the slices to oxotremorine or physostigmine, whereas the potency of atropine was independent of the agonist used.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Pharmacology and Experimental Therapeutics 06/1988; 245(2):658-63. · 3.89 Impact Factor
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    ABSTRACT: Dopamine D-1 receptor-stimulated cyclic AMP efflux from superfused rat neostriatal slices was strongly inhibited by the delta-opioid receptor agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE, 1 microM), and by the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 1 microM). Naloxone (0.1 microM) fully antagonized the inhibitory effect of DAGO, leaving that of DPDPE virtually unchanged. Preincubation of the slices with the irreversible delta receptor ligand, fentanyl isothiocyanate (FIT, 1 microM) did not affect the inhibitory effect of DAGO, but prevented that of DPDPE. Naloxone no longer antagonized the inhibitory effect of DAGO when the delta receptors were selectively and irreversibly blocked by FIT. These data indicate that FIT and naloxone, acting on delta and mu receptors, respectively, may share a common binding site, suggesting the involvement of a functional mu, delta-opioid receptor-complex.
    European Journal of Pharmacology 05/1988; 149(1-2):179-82. · 2.59 Impact Factor
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    ABSTRACT: Possible local interactions between noradrenergic and serotonergic systems in the dorsal raphe region of the rat were investigated by studying the effects of various drugs on depolarization (20 mmol/l K+)-induced release of [3H]5-hydroxytryptamine (5-HT) and [3H]noradrenaline (NA) in vitro using a superfusion method. Exogenous 5-HT did not influence the release of [3H]NA. However, NA (in the presence of 10 mumol/l desipramine) as well as the selective alpha 2-adrenoceptor agonists clonidine and oxymetazoline strongly inhibited [3H]5-HT release. The selective alpha 1-adrenoceptor agonists phenylephrine and methoxamine did not affect the release of either [3H]5-HT or [5H]NA. The inhibition by NA of both [3H]5-HT and [3H]NA release was not affected by the beta-adrenoceptor antagonist sotalol nor by the selective alpha 1-adrenoceptor antagonist prazosin. However, phentolamine and the selective alpha 2-adrenoceptor antagonists yohimbine and rauwolscine competitively antagonized the inhibitory effect of NA on [3H]NA release (respective pA2-values 7.5 and 8.3) and on [3H]5-HT release (respective pA2-values 7.7 and 8.2). Moreover, the release of [3H]NA and also, but to a lesser extent, that of [3H]5-HT were increased by the antagonists. It is concluded that the release of both 5-HT and NA in the dorsal raphe region may be subject to presynaptic inhibition by NA via activation of alpha 2-adrenoceptors.
    Archiv für Experimentelle Pathologie und Pharmakologie 04/1988; 337(3):255-60. · 2.15 Impact Factor
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    ABSTRACT: Opioid and D-2 receptor agonists inhibit adenylate cyclase activity in neostriatal slices and homogenates. In the present study we used cyclic AMP efflux from rat neostriatal tissue as a parameter to estimate the effects of these drugs on cyclic AMP formation. Both the mu-opioid receptor agonist morphine and the D-2 dopamine receptor agonist LY 171555 were able to inhibit the forskolin-stimulated cyclic AMP efflux. The effects of morphine and LY 171555 could be reversed by naloxone and sulpiride, respectively. These data indicate that measurements of cyclic AMP efflux from brain slices is an accurate reflection of the effects of receptor stimulation on adenylate cyclase activity.
    Neuropharmacology 08/1987; 26(7A):785-7. · 4.11 Impact Factor
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    ABSTRACT: Synaptosomes prepared from rat cerebral cortex and labeled with [3H]noradrenaline (NA) were superfused with calcium-free Krebs-Ringer-bicarbonate medium and exposed to 10 mM K+ plus 0.1 mM Ca2+ so that [3H]NA release was induced. 6,7-Dihydroxy-N,N-dimethyl-2-aminotetralin (TL-99) strongly inhibited synaptosomal K+-induced [3H]NA release (EC50 = 5-10 nM) by activating alpha 2-adrenoceptors. Release was also inhibited (maximally by 40-50%) by morphine (EC50 = 5-10 nM), [Leu5]enkephalin (EC50 = approximately 300 nM), [D-Ala2,D-Leu5]enkephalin (DADLE), and Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) (EC50 values = approximately 30 nM). In contrast to the mu-selective opioid receptor agonists morphine and DAGO, the highly delta-selective agonist [D-Pen2,D-Pen5]enkephalin (1 microM) did not affect [3H]-NA release. Furthermore, the inhibitory effect of DADLE, an agonist with affinity for both delta- and mu-opioid receptors, was antagonized by low concentrations of naloxone. The findings strongly support the view that, like alpha 2-adrenoceptors, mu-opioid receptors mediating inhibition of NA release in the rat cerebral cortex are localized on noradrenergic nerve terminals.
    Journal of Neurochemistry 05/1987; 48(4):1043-7. · 3.97 Impact Factor
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    ABSTRACT: D-1 dopamine receptor-stimulated cyclic AMP efflux from rat neostriatal slices (induced by 30 microM dopamine + 10 microM (-)sulpiride) was concentration-dependently reduced by morphine, [D-Ala-D-Leu]-enkephalin (DADLE), [D-Pen-D-Pen]enkephalin (DPDPE) and bremazocine. Naloxone (0.1 microM) selectively antagonized the inhibitory effect of (a submaximally effective concentration of) morphine, whereas ICI 174864 (0.75 microM) completely blocked the inhibitory effects of DADLE, DPDPE and bremazocine without affecting that of morphine, indicating a role of mu- as well as delta-opioid receptors. Upon simultaneous activation of D-1 dopamine receptors and delta-opioid receptors the (mu-receptor-mediated) inhibitory effect of morphine was abolished, while it was not changed following simultaneous activation of D-1 and (inhibitory) D-2 dopamine receptors. Cyclic AMP efflux induced by isoprenaline or adenosine was not affected by the opioids and that induced by vasoactive intestinal peptide (VIP) was inhibited by morphine and DADLE only. In the latter case naloxone, but not ICI 174864, antagonized the inhibitory effects. These data show that D-1 dopamine receptor-stimulated adenylate cyclase activity in rat neostriatum, but not that stimulated through other receptors, is inhibited by two pharmacologically distinct opioid receptor subtypes. It is speculated that these mu- and delta-opioid receptors share a common inhibitory guanine nucleotide binding protein and may represent closely associated recognition sites of a functional opioid receptor complex.
    Archiv für Experimentelle Pathologie und Pharmakologie 04/1987; 335(3):278-84. · 2.15 Impact Factor
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    ABSTRACT: Synaptosomes prepared from rat cerebral cortex and labeled with [3H]noradrenaline (NA) were superfused with calcium-free Krebs-Ringer-bicarbonate medium and exposed to 10 mM K+ plus 0.1 mM Ca2+ so that [3H]NA release was induced. 6,7-Dihydroxy-N,N-dimethyl-2-ami-notetralin (TL-99) strongly inhibited synaptosomal K+-in-duced [3H]NA release (EC50= 5–10 nM) by activating 2-adrenoceptors. Release was also inhibited (maximally by 40–50%) by morphine (EC50= 5–10 nM), [Leu5]enkephalin (EC50=∼300 nM), [d-Ala2,d-Leu5]enkephalin (DADLE), and Tyr-d-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) (EC50 values =∼30 nM). In contrast to the μ-selective opioid receptoragonists morphine and DAGO, the highly δ-selective agon ist [d-Pen2, dPen5]enkephalin (1 μM) did not affect [3H]-NA release. Furthermore, the inhibitory effect of DADLE, an agonist with affinity for both δ-and μ-opioid receptors, was antagonized by low concentrations of naloxone. The findings strongly support the view that, like 2-adrenocep-tors, μ-opioid receptors mediating inhibition of NA release in the rat cerebral cortex are localized on noradrenergic nerve terminals.
    Journal of Neurochemistry 03/1987; 48(4):1043 - 1047. · 3.97 Impact Factor
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    ABSTRACT: D-1 dopamine receptor-stimulated cyclic AMP efflux from rat neostriatal slices (induced by 30 M dopamine + 10 M (–)sulpiride) was concentration-dependently reduced by morphine, [abetd-Ala-abetd-Leu]-enkaphalin (DADLE), [d-Pen-abetd-Pen]enkephalin (DPDPE) and bremazocine. Naloxone (0.1 M) selectively antagonized the inhibitory effect of (a submaximally effective concentration of) morphine, whereas ICI 174864 (0.75 M) completely blocked the inhibitory effects of DADLE, DPDPE and bremazocine without affecting that of morphine, indicating a role of - as well as -opioid receptors. Upon simultaneous activation of D-1 dopamine receptors and b-opioid receptors the (-receptor-mediated) inhibitory effect of morphine was abolished, while it was not changed following simultaneous activation of D-1 and (inhibitory) D-2 dopamine receptors. Cyclic AMP efflux induced by isoprenaline or adenosine was not affected by the opioids and that induced by vasoactive intestinal peptide (VIP) was inhibited by morphine and DADLE only. In the latter case naloxone, but not ICI 174864, antagonized the inhibitory effects.These data show that D-1 dopamine receptor-stimulated adenylate cyclase activity in rat neostriatum, but not that stimulated through other receptors, is inhibited by two pharmacologically distinct opioid receptor subtypes. It is speculated that these - and -opioid receptors share a common inhibitory guanine nucleotide binding protein and may represent closely associated recognition sites of a functional opioid receptor complex.
    Archiv für Experimentelle Pathologie und Pharmakologie 01/1987; 335(3):278-284. · 2.15 Impact Factor
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    ABSTRACT: The effects of drugs known to enhance intracellular cyclic AMP levels on depolarization-induced [3H]norepinephrine release from superfused rat neocortical slices and synaptosomes were investigated. The adenylate cyclase activator forskolin, the membrane-permeating cyclic AMP analogues 8-bromo-cyclic AMP and dibutyryl cyclic AMP, as well as the phosphodiesterase inhibitors isobutylmethylxanthine and 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrolidone (ZK 62771) enhanced the electrically evoked release of [3H]norepinephrine from superfused rat brain neocortex slices. 8-Bromo-cyclic GMP was without effect on the electrically evoked release. When [3H]norepinephrine release was enhanced by prolonging the electrical pulse duration from 2 msec to 10 msec, the relative inhibitory effect of the Ca2+ channel blocker Cd2+ and the relative facilitatory effect of the K+ channel blocker 4-aminopyridine remained unaffected. In striking contrast, the relative facilitatory effects of forskolin and 8-bromo-cyclic AMP were strongly reduced, whereas the effect of ZK 62771 was almost doubled. When veratrine-induced release of [3H]norepinephrine from cortex synaptosomes was examined, the facilitatory effects of forskolin, 8-bromo-cyclic AMP, and ZK 62771 were even more pronounced than in brain slices. The data strongly support the hypothesis that a presynaptic adenylate cyclase system plays a facilitatory role in the stimulus-secretion coupling process in central noradrenergic nerve terminals.
    Journal of Neuroscience 11/1985; 5(10):2685-9. · 6.91 Impact Factor
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    ABSTRACT: At least three different families of endogenous opioid peptides, the enkephalins, endorphins and dynorphins, are present in the mammalian central nervous system (CNS). Immunocytochemical studies have demonstrated their localization in neurones, which supports the view that these peptides may have a role as neurotransmitter or neuromodulators. However, the target cells and cellular processes acted upon by the opioid peptides are still largely unknown. One possible function of neuropeptides, including the opioid peptides, may be presynaptic modulation of neurotransmission in certain neuronal pathways, for example, by inhibition or promotion of neurotransmitter release from the nerve terminals. Here we report that dynorphin and some benzomorphans potently and selectively inhibit the release of (radiolabelled) dopamine from slices of rat corpus striatum, by activating kappa-opioid receptors. In contrast, [Leu5]enkephalin and [D-Ala2, D-Leu5]enkephalin selectively inhibit acetylcholine release by activating delta-opioid receptors.
    Nature 01/1984; 308(5956):278-80. · 38.60 Impact Factor

Publication Stats

1k Citations
182.44 Total Impact Points

Institutions

  • 1987–2000
    • VU University Amsterdam
      • Faculty of Medicine/VU University Medical Center
      Amsterdam, North Holland, Netherlands
  • 1987–1997
    • University of the Free State
      • Department of Pharmacology
      Bloemfontein, Free State, South Africa
  • 1978–1992
    • University of Amsterdam
      • Department of Neurology
      Amsterdamo, North Holland, Netherlands
  • 1991
    • The University of Arizona
      Tucson, Arizona, United States