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Biomedical subjects

J C Stoof

Publications and source records attributed to J C Stoof.

At least 109 records · Page 6Linked to original sources
PubMed1984

Opposing roles for D-1 and D-2 dopamine receptors in regulating the excitability of growth hormone-producing cells in the snail Lymnaea stagnalis.

Dopamine hyperpolarizes growth hormone-producing cells (GHC) in the CNS of Lymnaea stagnalis. This effect of dopamine was mimicked by the D-2 receptor agonist LY 141865 and antagonized by the D-2 receptor antagonists (-)-sulpiride and YM 09151-2. SKF 38393, a selective D-1 receptor agonist, increased the excitability of the GHC. This effect was mimicked by intracellular injection of cyclic AMP and antagonized by the D-1 receptor antagonist SCH 23390. Dopamine (in the presence of (-)-sulpiride) also increased the excitability of the GHC. It is concluded that both a D-1 and a D-2 receptor regulate the electrical activity of the GHC in the CNS of Lymnaea stagnalis.

Animals↗
PubMed1984

The effects of SCH 23390, YM 09151-2, (+)- and (-)-3-PPP and some classical neuroleptics on D-1 and D-2 receptors in rat neostriatum in vitro.

The actions in vitro of SCH 23390, YM 09151-2 and both enantiomers of 3-PPP on D-1 and D-2 dopamine receptors were investigated in superfused rat neostriatal slices. For comparison the following neuroleptics of different chemical classes were incorporated in our investigations: (+)-bulbocapnine, clozapine, chlorpromazine, cis-flupenthixol, (-)-sulpiride and haloperidol. The increase in the efflux of cyclic AMP was used as a measure for D-1 receptor stimulation. The decrease in the K+-evoked release of [3H]acetylcholine was used as measure of D-2 receptor stimulation. None of the drugs stimulated the D-1 receptor. Only (+)-3-PPP stimulated the D-2 receptor. All other drugs, including (-)-3-PPP, behaved as antagonists on the D-2 receptor, YM 09151-2 being the most potent. SCH 23390 was the most potent antagonist on the D-1 receptor. Haloperidol, cis-flupenthixol and (+)-bulbocapnine showed an appreciable D-1 receptor blocking potency in our model, whereas the other drugs were inactive. We found SCH 23390 to be the most D-1 selective antagonist although the drug still displayed considerable potency on the D-2 receptor. YM 09151-2 was the most D-2 selective antagonist.

1-Methyl-3-isobutylxanthine↗
PubMed1984

SCH 23390 blocks D-1 and D-2 dopamine receptors in rat neostriatum in vitro.

The agonistic and antagonistic effects of the new compound SCH 23390 were tested in functional model systems for the D-1 dopamine receptor and for the D-2 dopamine receptor in vitro. In superfused rat neostriatal slices the increase in the efflux of cyclic AMP was used as a parameter for D-1 receptor stimulation. D-2 receptor stimulation was measured as the decrease in the K+-evoked release of [3H]-acetylcholine. SCH 23390 had no agonistic activity in these two models. SCH 23390 was a potent antagonist of the stimulating effect of dopamine in the D-1 receptor model (apparent pA2 = 7.28). SCH 23390 also antagonized the effect of the D-2 receptor agonist LY 141865 in the D-2 receptor model (apparent pA2 = 6.34). This D-2 receptor antagonism proved to be of a competitive nature.

1-Methyl-3-isobutylxanthine↗
PubMed1983

3-PPP antagonizes the in vitro effects of D-1 and D-2 dopamine receptor agonists in rat neostriatum.

3-PPP has been reported to be a selective dopamine autoreceptor agonist, a conclusion based on in vivo studies. In rat neostriatum in vitro however, 3-PPP antagonized concentration-dependently the stimulation of cyclic AMP efflux caused by the D-1 receptor agonist SKF 38393 and the inhibition of K+-induced [3H]acetylcholine release caused by the D-2 receptor agonist LY 141865. 3-PPP alone did not affect [3H]acetylcholine release or cyclic AMP efflux. When interpreting the effects of 3-PPP in vivo dopamine receptor antagonism should be considered.

Acetylcholine↗
PubMed1982

The effects of convulsant and anticonvulsant drugs on the release of radiolabeled GABA, glutamate, noradrenaline, serotonin and acetylcholine from rat cortical slices.

A possible presynaptic site of action of convulsant and anticonvulsant drugs has been evaluated by studying their effect on depolarization-induced transmitter release using radiolabeled GABA, glutamate, noradrenaline, serotonin and acetylcholine. The antiepileptic diphenylhydantoin (DPH) inhibited the release of noradrenaline and serotonin at concentrations that are antiepileptic in vivo. The release of the other transmitters was affected only with higher concentrations. Phenobarbital (PhB) reduced the release of all transmitters studied at concentrations much above the levels that are considered antiepileptic in vivo. Comparison with the anesthetic barbiturate pentobarbital (PB) further indicated that the presynaptic effects of PhB were related to its sedative rather than antiepileptic properties. Diazepam and sodium valproate had little effect; only GABA release was slightly reduced with diazepam at the highest concentration studied. The convulsants penicillin and pentylenetetrazole both increased the release of glutamate at concentrations that induce epileptiform activity in vivo or in vitro. Other transmitter systems were differentially affected by the two convulsants. A small increase of noradrenaline and serotonin release was observed with penicillin, but not with pentylenetetrazole. A presynaptic site of action for some, but not all, epileptogenic and antiepileptic drugs probably exists in addition to other, postsynaptic mechanisms. Glutamate is probably a major excitatory neurotransmitter in the brain and many physiological studies have suggested a role of excitatory pathways in the generation of epileptiform activity. The observed increase of glutamate release in the presence of two epileptogenic drugs observed in this in vitro study is in agreement with such a hypothesis.

Acetylcholine↗
PubMed1982

Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated efflux of cyclic AMP and K+-stimulated release of acetylcholine from rat neostriatum.

Two types of dopamine receptors whose stimulation affect cAMP efflux (and by inference formation) could be identified in rat neostriatum. One type of receptor, called D-1 receptor, increased cAMP efflux whereas stimulation of a second type of dopamine receptor, called D-2 receptor, was followed by a reduction in cAMP efflux induced by stimulation with a D-1 receptor agonist. D-2 receptor agonists inhibited the effects of D-1 receptor agonists on cAMP efflux in a non-competitive way. These inhibiting effects of D-2 receptor agonists occurred also in the absence of Ca2+-ions which could imply that some of the D-2 receptors are located on cells possessing D-1 receptors. The dopamine receptor mediating inhibition of the release of radiolabeled acetylcholine (ACh) in the neostriatum appeared to have the same pharmacological characteristics as the D-2 dopamine receptor mediating the inhibition of the D-1 receptor agonist induced cAMP efflux. Selective D-2 receptor agonists like LY 141865 and RU 24926 stimulated this receptor while the D-1 receptor agonist SKF 38393 was inactive. Effects of the selective D-2 receptor agonists could be antagonized by (-)-sulpiride, a selective D-2 receptor antagonist. Although the pharmacological characteristics of the dopamine receptors mediating inhibition of both ACh release and (D-1 dopamine receptor agonist induced) cAMP efflux appeared to be similar, drugs stimulating cAMP efflux did not affect ACh release or LY 141865 induced inhibition of ACh release from rat neostriatum. Therefore it is still questionable whether the dopamine receptor mediating inhibition of both ACh release and cAMP efflux is one and the same functional entity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1982

Stimulation of D2-dopamine receptors in rat neostriatum inhibits the release of acetylcholine and dopamine but does not affect the release of gamma-aminobutyric acid, glutamate or serotonin.

D1-dopamine receptor stimulation did not affect the K+-induced release of [3H]GABA, [3H]glutamate, [3H]serotonin, [3H]dopamine and [14C]acetylcholine from slices of rat neostriatum. D2-dopamine receptor stimulation did not change the release of [3H]GABA, [3H]glutamate and [3H]serotonin, but inhibited the release of both [3H]dopamine and [14C]acetylcholine; this inhibition was antagonized by (-)-sulpiride. The release-inhibiting dopamine autoreceptors and the post synaptic dopamine receptors mediating the inhibition of acetylcholine release appear to be pharmacologically similar and can be classified as D2-receptors.

Acetylcholine↗
PubMed1982

Biochemical and physiological studies of the beta-adrenoceptor and the D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland: a review.

The intermediate lobe (IL) of the rat pituitary gland responds to catecholamines. Catecholamines interacting with the beta-adrenoceptor stimulate adenylate cyclase activity, enhance cyclic AMP formation and thereby trigger the release of alpha-melanocyte-stimulating hormone (alpha-MSH). Catecholamines interacting with a D-2 dopamine receptor (in the classification schema of Kebabian and Calne) diminish adenylate cyclase activity and thereby decrease the capacity of IL cells to synthesize cyclic AMP. Dopaminergic agonists also inhibit the release of alpha-MSH from IL cells. The homogeneity of the IL facilitates biochemical investigations of this tissue.

Animals↗
PubMed1982

D-2 dopamine receptor-mediated inhibition of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland requires guanosine 5'-triphosphate.

After treatment with cholera toxin, homogenates of intact intermediate lobe (IL) tissue of rat pituitary gland synthesized more cAMP than did homogenates of untreated IL tissue, and only in the presence of GTP did dopamine or apomorphine diminish the elevated adenylate cyclase activity in homogenates of cholera toxin-treated IL tissue. Furthermore, when tested on cholera toxin-treated IL tissue, 5'-guanylyl imidodiphosphate [Gpp(NH)p] and two other nonhydrolyzable analogs of GTP inhibited adenylate cyclase activity in the absence of either a dopaminergic agonist or GTP; GTP reversed the Gpp(NH)p-induced inhibition of adenylate cyclase activity. Apomorphine, a dopaminergic agonist, abolished the ability of GTP to reverse the inhibition by Gpp(NH)p; this effect of apomorphine was prevented by fluphenazine, a dopaminergic antagonist. Sodium fluoride inhibited adenylate cyclase activity to approximately the same level obtained with GTP and apomorphine. In addition, apomorphine decreased cAMP accumulation and alpha MSH release from dispersed IL cells pretreated with cholera toxin.

Adenylyl Cyclase Inhibitors↗
PubMed1980

Activation of presynaptic alpha-noradrenaline receptors in rat brain by the potent dopamine-mimetic N,N-dipropyl-5,6-ADTN.

Rat cerebral cortex slices labeled with 3H-noradrenaline (NA) were superfused and 3H-NA release was induced with 20 mM K+. The release of 3H-NA was not affected by DA (1 micro M), but was inhibited by the 2-aminotetralins, 5,6-ADTN and N,N-dipropyl-5,6-ADTN (at a concentration of 1 micro M) by about 27% and 65%, respectively. The inhibitory effect of N,N-dipropyl-5,6-ADTN was concentration-dependent (3 x 10(-8) to 3 x 10(-7) M) and was antagonized by phentolamine but not by fluphenazine. The data indicate that, in addition to activating dopamine receptors, N,N-dipropyl-5,6-ADTN stimulates presynaptic alpha-NA receptors.

Animals↗
PubMed1980

An evaluation of the young dopamine-lesioned rat as an animal model for minimal brain dysfunction (MBD).

Three main symptoms of minimal brain dysfunction (MBD), a common disorder in children, are hyperactivity, learning disabilities, and attention deficits. Drugs like amphetamine and methylphenidate have been demonstrated to produce a significant behavioral improvement in these children. The behavioral response of young rats (3--4 weeks), with selective lesioning of the central dopaminergic system, to a novel environment was analyzed. Both the frequencies and durations of eight mutually exclusive and complementary behavioral categories were scored. By analyzing the behavior in this way it appeared that considerable hyperactivity and learning disabilities could be demonstrated in these rats. Moreover, the bout length of some behavioral categories was somewhat shortened, which might be an indication of deficits in attention. However, treatment of the animals with amphetamine did not produce any "therapeutic" effect on the three symptoms. Since pharmacotherapeutic support is, in our opinion, a "conditio sine qua non" for the validity of the model, we do not believe that the young DA-lesioned rat is an appropriate animal model for MBD.

Animals↗
PubMed1979

GABA modulates the release of dopamine and acetylcholine from rat caudate nucleus slices.

The effects of GABA on depolarization-induced (26 mM K+) release of radiolabeled dopamine (DA) and acetylcholine (ACh) from slices of rat caudate nucleus were examined with a superfusion method. GABA, in concentrations of 10(-5)--10(-3) M, dose-dependently enhanced the release of DA, either accumulated by high-affinity uptake or synthesized from 14-C-tyrosine. In contrast, the release of ACh was reduced by GABA. This reduction appeared to be caused by the increase in DA-release. These effects of GABA decreased from the caudal to rostral part within the caudate nucleus, an order which parallels the distribution of endogenous GABA and glutamic acid decarboxylase. However, GABA had little, if any, effect in the nucleus accumbens. Since it was difficult to antagonize the effects of GABA on DA and ACh release with bicuculline or picrotoxin, it remains uncertain whether these effects were mediated via GABA receptors. In view of the high endogenous GABA level in the caudate nucleus it is concluded that GABA may be one of the local factors involved in the control of the amount of transmitter that will be released from dopaminergic varicosities upon depolarization.

Acetylcholine↗