Search PubMed⌕ Search

Biomedical subjects

J C Stoof

Publications and source records attributed to J C Stoof.

At least 73 records · Page 4Linked to original sources
PubMed1992

Dopamine D2 receptor stimulation differentially affects voltage-activated calcium channels in rat pituitary melanotropic cells.

1. Whole-cell voltage clamp recordings were made from 141 rat pituitary melanotropic cells in short-term, serum-free, primary culture. The effects of the dopamine D2 receptor agonist, LY 171555, on sodium, potassium and barium currents were investigated. 2. Application of 1 microM-LY 171555 did not affect the inward sodium and outward potassium currents. 3. Application of LY 171555 reversibly inhibited barium currents, with the strongest inhibition on the early inward current. The effect was dose dependent (IC50 = 4 x 10(-8) M), maximal inhibition of the total current was 30% and the LY 171555-induced block (1 microM) was reversibly antagonized by (+/-)sulpiride (4 microM). 4. Using barium-selective saline solutions, different types of barium current (T, N, and two L components) were identified on the basis of their voltage-dependent kinetics. Their relative amplitudes differed between cells. 5. The T-type current activated at potentials positive to -60 mV, reaching peak amplitude between -20 and -10 mV. At -30 mV, this current was inhibited up to 30% by 1 microM-LY 171555. The time constants of activation (10-3 ms) and inactivation (50-20 ms) as well as the voltage dependence of inactivation (potential of half-maximal inactivation (H), -61 mV; slope factor (S), 4.9 mV) were not affected by LY 171555 application. 6. A rapidly inactivating (time constants 100-50 ms), high threshold current component was identified as an N-type current. This current activated at command potentials positive to -30 mV and reached a maximal amplitude at +10 mV. The steady-state inactivation was described by a single Boltzmann equation with H = -65 mV and S = 11.7 mV. Application of 1 microM-LY 171555 completely suppressed this current. 7. The slowly inactivating (time constants > 1500 ms), high-threshold, L-type current displayed the same voltage dependence of activation as the N current. The voltage dependence of inactivation was modelled by the sum of two Boltzmann equations (L1: H1 = -45 mV, S1 = 13.0 mV; L2:H2 = -11 mV, S2 = 6.0 mV), indicating the existence of two L channel populations. Neither time course, nor voltage dependence of inactivation were influenced by LY 171555. However, LY 171555 induced a slow-down in the time course of activation, which necessitated the use of two time constants to model the activation kinetics. One of these (approximately 2 ms) was also observed under control conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Regional differences in the regulation of acetylcholine release upon D2 dopamine and N-methyl-D-aspartate receptor activation in rat nucleus accumbens and neostriatum.

The effect of D2 dopamine receptor activation on either the electrically, or N-methyl-D-aspartate induced release of radiolabeled acetylcholine (ACh) was investigated in different areas of the nucleus accumbens and the neostriatum of rats, by using a superfusion technique. Sequential slices of 100 microns were chopped along either a rostrocaudal, mediolateral or dorsoventral axis. In every slice the effect of a supramaximal concentration of the selective D2 receptor agonist quinpirole on the release of ACh was measured. In the entire neostriatum the release of ACh was reduced by approximately 70% in the presence of quinpirole. By contrast, in the nucleus accumbens, a gradual decrease in the inhibitory effect of quinpirole on the release of ACh was observed along both the rostral-to-caudal and the lateral-to-medial axes. Whereas in the rostrolateral part a 50% inhibition could be observed, in the caudomedial part no significant inhibition could be detected. Also the N-methyl-D-aspartate induced release of ACh was smaller in the caudomedial part as compared to the rostrolateral part of the nucleus accumbens. It is concluded that the nucleus accumbens is a very heterogeneous structure with respect to the regulation of the release of ACh by D2 dopamine and N-methyl-D-aspartate receptor activation.

Acetylcholine↗
PubMed1991

Differences in the regulation of acetylcholine release upon D2 dopamine and N-methyl-D-aspartate receptor activation between the striatal complex of reptiles and the neostriatum of rats.

Activation of the N-methyl-D-aspartate (NMDA) receptor increases and that of the D2 dopamine (DA) receptor inhibits the release of acetylcholine (ACh) from mammalian neostriatal tissue. Similar effects have been described in the ventral striatum of the rat, however, in the caudomedial part of the nucleus accumbens, D2 receptor activation does not inhibit the release of ACh. Likewise, the NMDA-induced stimulation of the release of ACh in this part of the striatum is much smaller. In the present study we demonstrated that in the striatal complex or striatum of reptiles D2 receptor activation did not result in an inhibition of the release of ACh, whereas the release of DA could be inhibited to a significant extent. These findings indicate that, although D2 receptors are present in the striatum of reptiles, these receptors do not regulate the release of ACh in this brain structure. We observed in the striatum of reptiles a potassium induced and calcium-dependent release of [3H]D-aspartate indicating a neurotransmitter role for aspartate or glutamate (GLU). However GLU and NMDA have only a marginal effect on the release of ACh in the striatum of the reptiles as compared to the effects in the neostriatum of the rat. It is concluded that with respect to the effects of D2 and NMDA receptor activation on the release of ACh, the striatum of reptiles bears most similarity to the caudomedial part of the nucleus accumbens.

Acetylcholine↗
PubMed1991

Sustained activation does not desensitize the dopamine D2 receptor-mediated control of evoked in vitro release of radiolabeled acetylcholine from rat striatum.

Striatal acetylcholine release is decreased on activation of D2 dopamine receptors. In the present study, it was investigated whether sustained activation of these receptors would reduce their capacity to mediate this effect. It was shown that activation for up to 2 h with high concentrations of either the endogenous ligand, dopamine, or the selective D2 receptor agonist, LY 171555, did not induce desensitization of the D2 receptor-mediated inhibited of electrically evoked [3H]acetylcholine release from rat striatal tissue slices.

Acetylcholine↗
PubMed1991

Localization of dopamine and its relation to the growth hormone producing cells in the central nervous system of the snail Lymnaea stagnalis.

The distribution of dopamine in the central nervous system of the pond snail Lymnaea stagnalis was investigated by using immunocytochemistry and HPLC measurements. With both methods it was demonstrated that dopamine is predominantly present in the cerebral and pedal ganglia. The dopamine-immunoreactivity was mainly observed in nerve-fibers in the neuropile of the ganglia. Relatively few dopamine-immunopositive cell bodies (diameters 10-30 microns) were found. A large cell in the right pedal ganglion (the so-called RPeD1) stained positively with the dopamine antibody. It has previously been demonstrated that the growth hormone producing cells (GHCs) possess dopamine receptors on their cell bodies. However, dopamine-immunopositive fibers were observed only in the vicinity of the GHC nerve-endings and not close to the GHC cell bodies.

Animals↗
PubMed1991

Voltage-activated currents through calcium channels in rat pituitary melanotrophic cells.

Voltage-gated currents through Ca channels in rat melanotrophs in short-term primary culture were investigated in whole cell voltage clamp recordings, using Ba2+ ions as charge carrier. At potentials higher than -50 mV a transient current (It) was activated, which inactivated entirely during a 150-ms command pulse and reached a maximal amplitude at -10 mV. At potentials higher than -20 mV a second component (Is) appeared, which inactivated slowly and had its maximal amplitude between 0 and +10 mV. The relative amplitudes of It and Is differed between cells. Application of 40 microM NiCl2 reversibly blocked It while leaving Is intact, whereas 20 microM CdCl2 reversibly blocked Is, but not It. Nifedipine blocked Is concentration dependently, but did not affect It. The steady state inactivation of It occurred between -80 and -40 mV. The steady-state inactivation curve of Is was located between -60 and 0 mV. The latter inactivation curve showed two phases, which were fitted best by the sum of two Boltzmann equations, suggesting the existence of two populations of Is channels.

Action Potentials↗
PubMed1990

Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum.

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.

Adenylyl Cyclases↗
PubMed1990

Indications for a hormonal function of dopamine in the central nervous system of the snail Lymnaea stagnalis.

In the present paper we collected evidence for the occurrence of D2-like dopamine receptors on the cell bodies of the neuroendocrine growth hormone-producing cells (GHCs) in the central nervous system (CNS) of the snail Lymnaea stagnalis. Measurements of the membrane potential of GHCs in situ as well as isolated GHCs revealed that stimulation of these dopamine receptors results in a hyperpolarization. Although immunohistochemical analysis of the CNS of L. stagnalis clearly revealed the occurrence of dopamine containing cells and nerve fibers, no projections of dopamine immunopositive fibers to the GHC cell bodies could be observed. By using HPLC with electrochemical detection we found that the blood concentration of dopamine in L. stagnalis is in the range of concentrations hyperpolarizing GHCs in vitro (0.1-10 microM). On the basis of these findings it is proposed that dopamine is involved in hormonal communication in the CNS of L. stagnalis.

Animals↗
PubMed1990

The quinolinic acid hypothesis in Huntington's chorea.

In the central nervous system and particularly in the striatum of patients with Huntington's disease (HD) a dramatic cell loss can be observed. Animal models of HD are based on intrastriatal injection of excitatory amino acids (EAAs). Stimulation of EAA receptors for a prolonged period of time degenerates the cells on which the EAA receptors are located, a phenomenon known as excitotoxicity. Several categories of EAA receptors, viz. quisqualate, kainate and N-methyl-D-aspartate (NMDA), have been identified in the central nervous system. Interestingly, quinolinic acid, a metabolite of tryptophan along the kynurenine pathway, appeared to be an agonist on the NMDA receptor and a potent excitotoxin. Indications have been reported, although still controversial, for derangements in the formation of quinolinic acid to occur in the brains of patients with HD. Based on these studies the likeliness of a role for quinolinic acid in the etiology of HD is evaluated.

Brain↗
PubMed1990

D-2 dopamine autoreceptor selective drugs: do they really exist?

The catecholamine dopamine plays an important role as a neurotransmitter or neurohormone in the brain and pituitary gland. Dopamine exerts its effects through activation of two types of receptors called D-1 and D-2. These receptors are distinguished by their different pharmacological characteristics and signal transduction mechanism(s). Release of dopamine inhibits the activity of dopaminergic neurons through activation of so-called dopamine autoreceptors which are of the D-2 type. In general, these receptors occur both in the soma-dendritic region of the dopaminergic neuron, where they are involved in the inhibition of the firing rate and on the dopaminergic terminals where they mediate the inhibition of dopamine synthesis and release. D-2 receptors occur also on the target cells of dopaminergic neurons both in the brain (postsynaptic D-2 receptors) and pituitary gland. On the basis of data gathered from in vivo (behavioral- as well as electrophysiological) studies it has been concluded that D-2 agonists are much more potent at dopamine autoreceptors as compared to postsynaptic D-2 receptors, indicating the possibility of a pharmacological distinction between these differentially located D-2 receptors. This concept led to the introduction of a whole group of drugs allegedly displaying a selective agonist profile at the dopamine autoreceptor. In contrast, biochemical (in vitro) studies with brain tissue as well as the pituitary gland, did not reveal any significant difference between the pharmacological profiles of autoreceptors and postsynaptic D-2 receptors. In the present minireview a balanced discussion is presented of these in vivo and in vitro findings and it is concluded that both autoreceptors as well as postsynaptic D-2 receptors are similar if not identical entities.

Animals↗
PubMed1990

Muscarinic receptor activation attenuates D2 dopamine receptor mediated inhibition of acetylcholine release in rat striatum: indications for a common signal transduction pathway.

In the present investigations, we used a superfusion system to study the effect of simultaneous activation of D2 dopamine receptors and so-called muscarinic "autoreceptors" on the K(+)-evoked in vitro release of [3H]acetylcholine from rat striatal tissue slices. Activation of D2 receptors with the selective agonist LY 171555 (0.01-1 microM) clearly decreased the evoked release of [3H]acetylcholine. This effect was markedly attenuated in the presence of either the selective muscarinic receptor agonist oxotremorine (3 microM) or the cholinesterase inhibitor physostigmine (1 microM). Conversely, D2 receptor activation with LY 171555 (1 microM) completely abolished the muscarinic receptor mediated inhibition of evoked [3H]acetylcholine release induced by oxotremorine (0.03-10 microM). These results show that the inhibitory effects of D2 dopamine receptor and muscarinic receptor activation on striatal acetylcholine release are non-additive and therefore are interdependent processes. In addition, we investigated some aspects of the signal transduction mechanism by which the muscarinic receptor mediates inhibition of K(+)-evoked in vitro release of [3H]acetylcholine from rat striatal tissue slices. It appeared that the effect of muscarinic receptor activation was not significantly influenced either by a lowering of the extracellular Ca2+ concentration from the usual 1.2-0.12 mM or by an increase of the intracellular cyclic adenosine-3',5'-monophosphate content. However, increasing extracellular K+ strongly decreased the inhibition of evoked [3H]acetylcholine release mediated by activation of muscarinic receptors. This set of results indicates that the muscarinic "autoreceptor" mediates the decrease of depolarization induced [3H]acetylcholine release from rat striatum to a large extent through stimulation of K+ efflux (opening of K+ channels) in a cyclic adenosine-3',5'-monophosphate independent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Alpha 2-adrenoceptor-mediated modulation of noradrenaline release is decreased in vas deferens but not in cerebral cortex of diabetic rats.

In the present study, a superfusion method was used to investigate the alpha 2-adrenoceptor mediated modulation of the electrically evoked release of radiolabeled noradrenaline in vas deferens and cerebral cortex slices of streptozotocin-diabetic and control rats 8-10 weeks after the induction of diabetes. Stimulation of alpha 2-adrenoceptors led to a significantly smaller inhibition of radiolabeled noradrenaline release in the vas deferens of diabetic rats as compared to control rats. In the cerebral cortex no such difference was detected. It is concluded that these effects could be due to a decrease in the number of presynaptic alpha 2-adrenoceptors in the vas deferens of diabetic rats. The results of this study show that the superfusion technique offers a simple possibility to obtain information about the functional integrity of noradrenergic neurons in the peripheral nervous system and central nervous system in diabetes mellitus. Moreover, the results provide an indication for a different time scale in the development of neuropathy in the peripheral and central nervous system of streptozotocin-diabetic rats.

Animals↗
PubMed1989

Stimulation of D-2 dopamine receptors decreases the evoked in vitro release of [3H]acetylcholine from rat neostriatum: role of K+ and Ca2+.

Reportedly, stimulation of D-2 dopamine receptors inhibits the depolarization-induced release of acetylcholine from the neostriatum in a cyclic AMP-independent manner. In the present study, we investigated the role of K+ and Ca2+ in the D-2 receptor-mediated inhibition of evoked [3H]acetylcholine release from rat striatal tissue slices. It is shown that the D-2 receptor-mediated decrease of K+-evoked [3H]acetylcholine release is not influenced by the extracellular Ca2+ concentration. However, increasing extracellular K+, in the presence and absence of Ca2+, markedly attenuates the effect of D-2 stimulation on the K+-evoked [3H]acetylcholine release. Furthermore, it is shown that activation of D-2 receptors in the absence of Ca2+ also inhibits the veratrine-evoked release of [3H]acetylcholine from rat striatum. These results suggest that the D-2 dopamine receptor mediates the decrease of depolarization-induced [3H]acetylcholine release from rat striatum primarily by stimulation of K+ efflux (opening of K+ channels) and inhibition of intracellular Ca2+ mobilization.

Acetylcholine↗
PubMed1989

Restricted usefulness of tetraethylammonium and 4-aminopyridine for the characterization of receptor-operated K+-channels.

1. Recently, we suggested that the D2-dopamine receptor involved in the inhibition of evoked [3H]-acetylcholine release from rat striatum is coupled to K+-channels. 2. In the present study, an attempt was made to elucidate further the role of these K+-channels, using the K+-channel blocking agents tetraethylammonium and 4-aminopyridine. With a superfusion method, the effects of both drugs on the D2-dopamine receptor-mediated inhibition of the electrically evoked release of [3H]-acetylcholine from rat striatal tissue slices was investigated. 3. Both tetraethylammonium (30 mM) and 4-aminopyridine (0.1 mM) significantly stimulated the electrically evoked release of [3H]-acetylcholine and completely abolished the effect of the selective D2-receptor agonist LY 171555 (1 microM) on evoked acetylcholine release. In addition, tetraethylammonium (0.03-30 mM) and 4-aminopyridine (0.003-1 mM) strongly increased the basal (non-evoked) release of radioactivity in a concentration-dependent manner. The results suggest that the effect of the drugs on the basal release of radioactivity and on the electrically evoked release of acetylcholine cannot exclusively be explained by their action on K+-channels. 4. Furthermore, with the use of a receptor binding assay, data were obtained on the affinity of tetraethylammonium and 4-aminopyridine for D2-receptors and various other neurotransmitter recognition sites. At concentrations in which both drugs are known to block K+-channels, they were found to inhibit the specific binding of selective radioligands to their respective recognition sites. 5. It is concluded that due to their 'side-effects', both tetraethylammonium and 4-aminopyridine are of only limited value in the investigation of the alleged interaction between neurotransmitter receptors and K+-channels.

4-Aminopyridine↗
PubMed1988

Further analysis of the neuropharmacological profile of 9-amino-1,2,3,4-tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer's disease.

In a recent study we have documented the acetylcholinesterase and outward K+-current inhibiting activity of 9-amino-1,2,3,4-tetrahydroacridine (THA), a drug reportedly active in the treatment of Alzheimer patients. In the present study we investigated the effects of THA on the uptake and release of radiolabeled NA, DA and 5-HT. THA concentration-dependently inhibited the uptake of these monoamines with IC-50 values of approximately 1, 7 and 2 microM respectively. Release studies of these radiolabeled monoamines from control and reserpine pretreated tissue revealed that the THA-induced uptake inhibition does not occur at the level of the axonal membrane but at the level of the monoaminergic storage granules. In addition the affinity of THA for alpha-1, alpha-2 and beta-adrenoceptors, for D-2 dopamine, S-1a and S-2 serotonin and for muscarinic receptors was investigated. It appeared that in concentrations up to 1 microM THA did not display any affinity towards these receptors. It is concluded from these experiments that the effects of THA on monoaminergic neurotransmission might contribute to the alleged therapeutic action of THA in Alzheimer's disease.

Alzheimer Disease↗