Biomedical subjects

D H Versteeg

Publications and source records attributed to D H Versteeg.

At least 19 recordsLinked to original sources

PubMed1992

Effect of SCH 23390 and quinpirole on novelty-induced grooming behaviour in spontaneously hypertensive rats and Wistar-Kyoto rats.

Grooming behaviour induced by exposure to a novel environment was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The dopamine D1 receptor antagonist, SCH 23390, and the dopamine D2 receptor agonist, quinpirole, were used to study brain dopamine systems in these rat strains, via their effects on grooming behaviour. The total grooming behaviour displayed in a 50-min observation period was significantly lower in SHR than in WKY. Except for the paw licking component no differences between the two strains were observed in the separate behavioural elements of grooming behaviour. SCH 23390 and quinpirole were found to suppress novelty-induced grooming behaviour of both strains. In SHR, grooming behaviour was less suppressed by SCH 23390, whereas the suppression by quinpirole was more pronounced than in WKY. These results indicate that there are alterations in central dopamine systems in SHR, probably involving changes both in dopamine D1 and D2 receptor mechanisms in the brain.

Animals↗

PubMed1992

Characterization of the inhibitory effect of adrenocorticotropin/melanocyte-stimulating hormone-like peptides on the binding of dopamine receptor ligands to the dopamine D2 receptor in vitro.

Adrenocorticotropin (ACTH)-(1-24) decreased the binding of the dopamine D2 agonist [3H]N-n-propylnorapomorphine [3H](NPA) to the dopamine D2 receptor in rat striatal membranes in vitro. The association and dissociation of [3H]NPA to the dopamine D2 receptor was inhibited by ACTH-(1-24), suggesting an apparent competitive interaction between ACTH-(1-24) and the binding of [3H]NPA. ACTH-(1-24) was able to inhibit the binding of the dopamine D2 receptor antagonist [3H]spiperone to the dopamine D2 receptor, both in the high- and the low-affinity state. These observations suggest a G-protein-independent mechanism of action. The inhibitory effect of ACTH-(1-24) and ACTH-(7-16)-NH2 was diminished after the addition of polylysine chains, presumably via a blockade of the attachment sites for ACTH-(1-24) on the dopamine D2 receptor. The effect of ACTH-(1-24) on membrane fluidity and on the inhibition of the binding of [3H]NPA to the dopamine D2 receptor appeared to be unrelated because lowering the incubation temperature from 25 degrees C to 4 degrees C, which causes a strong decrease of membrane fluidity, did not diminish the effect of ACTH-(1-24) on the binding of [3H]NPA to the dopamine D2 receptor. Furthermore, in both young and old rats, whose membranes are reported to differ in lipid composition and membrane fluidity, ACTH-(1-24) inhibited the binding of [3H]NPA to the dopamine D2 receptor to nearly the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1991

Effect of the dopamine D2 receptor agonist quinpirole on the in vivo release of dopamine in the caudate nucleus of hypertensive rats.

Using an in vivo microdialysis method, we found that the extracellular concentrations of dopamine and its main metabolite dihydroxyphenylacetic acid (DOPAC) were lower in the caudate nucleus of 8-week-old spontaneously hypertensive rats (SHR) than in the same area of age-matched normotensive Wistar-Kyoto rats (WKY). No differences in the extracellular concentrations of dopamine and DOPAC were found between renal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats when compared to their respective controls. After subcutaneous administration of the dopamine D2 receptor agonist quinpirole (10, 33 and 100 micrograms/kg), the amount of dopamine and DOPAC in the dialysates was diminished dose dependently. The quinpirole-mediated inhibition of dopamine release was more pronounced in SHR than in WKY, whereas inhibition of the extracellular DOPAC concentration was not different. Compared to WKY, the dose-response curve for the inhibition of dopamine release by quinpirole was shifted to the left in SHR and the maximal inhibition in response to the highest dose was significantly greater. Renal and DOCA-salt hypertensive rats showed no differences in the quinpirole-induced inhibition of the extracellular concentrations of striatal dopamine and DOPAC compared to their controls. The present findings on changes in dopaminergic neurotransmission and D2 autoreceptor-mediated modulation of dopamine release in genetically hypertensive rats but not in rats with experimentally induced hypertension provide further evidence for the hypothesis that alterations in the nigrostriatal dopamine system may be involved in the initiation of the development of spontaneous hypertension.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

ACTH/MSH-like peptides inhibit the binding of dopaminergic ligands to the dopamine D2 receptor in vitro.

ACTH-(1-24) decreased the binding of the dopamine D2 receptor agonist, [3H]N-propylnorapomorphine ([3H]NPA), to rat striatal membranes in a concentration-dependent manner, with a Ki of 5 x 10(-7) M. Saturation curves for [3H]NPA binding in the presence of increasing concentrations of ACTH-(1-24) were performed. Scatchard analysis in the presence of ACTH-(1-24) revealed an increased dissociation constant (Kd), while the binding capacity (Bmax) was not affected by the peptide, suggesting an apparent competitive interaction between ACTH-(1-24) and [3H]NPA. ACTH-(1-24) also reduced the binding of the dopamine D2 receptor antagonist [3H]spiperone to striatal membranes, with a Ki of 10(-6) M. Much higher concentrations of ACTH-(1-24), up to 10(-4) M, were needed for the displacement of appropriate radiolabelled ligands from dopamine D1 receptors, serotonin 5-HT1A, serotonin 5-HT1B, muscarinic M1 acetylcholine and histamine H1 receptors. ACTH-(1-24) also inhibited the binding of [3H]spiperone to dopamine D2 receptors in membranes of the pituitary gland, the septum and the substantia nigra. ACTH-(1-39) and most ACTH fragments and analogs were less potent than ACTH-(1-24) in displacing [3H]NPA from the dopamine D2 receptor in striatal membranes. In general there was a relationship between displacing potency and chain length. ACTH-(7-16)-NH2 and benzyloxycarbonyl-ACTH-(8-16)-NH2, however, were more potent than ACTH-(1-24) in reducing the binding of [3H]NPA to dopamine D2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1991

The electrically stimulated release of [3H]noradrenaline from nucleus tractus solitarii slices in vitro is modulated via mu-opioid receptors.

The electrically stimulated release of [3H]noradrenaline ([3H]NA) from slices of the nucleus tractus solitarii (NTS) from the rat in vitro was inhibited by the alpha 2-adrenoceptor agonist, clonidine, in a concentration-dependent manner and enhanced by the alpha 2-adrenoceptor antagonist, yohimbine. Phenylephrine, isoprenaline, carbachol, quinpirole and SKF 38393, all at 10(-6) M, did not affect the stimulus-evoked release of [3H]NA. The opioid peptides, alpha- and gamma-endorphin, did not have a significant effect on the stimulus-evoked release of [3H]NA; however, beta-endorphin reduced it in a concentration-dependent manner. [Leu5]Enkephalin also reduced [3H]NA release, but higher concentrations were necessary. The selective delta opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), as well as the selective kappa opioid receptor agonist, U-69593, were not effective. The selective mu opioid receptor agonist, [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO), concentration dependently reduced the stimulus-evoked release of [3H]NA to the same extent as beta-endorphin did. Naloxone, while having no effect on stimulus-evoked [3H]NA release, antagonized the effect of DAGO. These results corroborate that the release of NA from noradrenergic terminals in the NTS region of the medulla oblongata of the rat is modulated via alpha 2-adrenoceptors and suggest that the release of NA in the NTS in rats is also modulated via mu opioid receptors.

Adrenergic alpha-Agonists↗

PubMed1991

Stimulus-evoked release of tritiated monoamines from rat periaqueductal gray slices in vitro and its receptor-mediated modulation.

The periaqueductal gray is a brain region of considerable interest. It is innervated by monoamine-containing neurons as well as by a variety of peptidergic fiber systems, and it participates in the regulation of various functions. Virtually nothing is known about monoamine release in the periaqueductal gray and its receptor-mediated modulation. We therefore studied the release of radioactivity from periaqueductal gray slices preloaded with tritriated monoamines, using an in vitro superfusion method. The release of radioactivity from superfused periaqueductal gray slices after preloading of the tissue with [3H]noradrenaline increased upon electrical stimulation in a frequency-dependent manner. The stimulus-evoked release of radioactivity was Ca(2+)-dependent. Clonidine reduced and yohimbine enhanced the release. The inhibition curve for the effect of clonidine was shifted to the right in the presence of 10(-6) M yohimbine. While phenylephrine, isoprenaline, SK & F 38393, quinpirole, carbachol, [Arg8]vasopressin, alpha-MSH and ACTH-(1-24), at a concentration of 10(-6) M, did not influence the electrically evoked release of radioactivity, [Leu5]enkephalin reduced it. The selective mu-opioid receptor agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin and [D-Arg2,Lys4]-demorphin-(1----4)-amide reduced the release of radioactivity, whereas the selective delta opioid receptor agonist [D-Pen2,D-Pen5] enkephalin and the selective kappa opioid receptor agonist U-69593 had no effect. In the presence of naloxone, which by itself had no effect on the release of radioactivity, the effect of [D-Arg2,Lys4]dermorphin-(1-4)-amide was abolished. These results show that the release of noradrenaline from periaqueductal gray slices is via a Ca(2+)-dependent exocytotic process, and that it is modulated through alpha 2-adrenoceptors as well as via mu-opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Role of brain dopamine systems in the development of hypertension in the spontaneously hypertensive rat.

We studied the role of central dopamine in the development of hypertension. Earlier work had shown that depletion of brain dopamine can inhibit the age-related rise in blood pressure in spontaneously hypertensive rats (SHR). In an open-field test, locomotor activity of Wistar-Kyoto controls was inhibited by haloperidol, apomorphine and sulpiride, but these drugs had less effect in SHR. The stimulation-evoked release of [3H]-dopamine from slices of the striatum of SHR was smaller than that from slices of WKY. The inhibition of the stimulation-evoked release of [3H]-dopamine by quinpirole was greater in SHR than in WKY. The results from the lesion experiments and from the behavioural activity studies would suggest an enhanced release of central dopamine in SHR, which might contribute to the development of hypertension in these animals. However, the in vitro release experiments (and subsequent in vivo microdialysis experiments) do not support such an enhanced release but rather showed decreased release of striatal dopamine in SHR.

Animals↗

PubMed1990

Evidence for a relationship between B-50 (GAP-43) and [3H]noradrenaline release in rat brain synaptosomes.

Phosphorylation of the neuron-specific substrate of protein kinase C (PKC), B-50 (GAP-43), was studied parallel with noradrenaline release in rat brain synaptosomes. Both could be evoked by treating the synaptosomes with high K+ or veratridine. Phorbol 12,13-dibutyrate enhanced depolarization-induced B-50 phosphorylation and noradrenaline release. To investigate the involvement of PKC-mediated B-50 phosphorylation in noradrenaline release, we applied a variety of kinase inhibitors. Prior to measuring the effects of these inhibitors in intact synaptosomes, we determined their effectivity and specificity in a membrane phosphorylation assay. H-7 most specifically inhibited PKC-dependent phosphorylation, whereas calmidazolium inhibited calmodulin-dependent phosphorylation. Polymyxin B affected both protein kinase systems. Only polymyxin B effectively inhibited noradrenaline release in the intact synaptosomes. We conclude that PKC as well as calmodulin-dependent processes are important for the release event. Data are discussed in view of the presumed function of B-50 as a calmodulin-binding protein.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1990

Electrically stimulated [3H]dopamine and [14C]acetylcholine release from nucleus caudatus slices: differences between spontaneously hypertensive rats and Wistar-Kyoto rats.

Using an in vitro superfusion method it was found that nucleus caudatus slices of 8- and 12-week-old spontaneously hypertensive rats (SHR) release significantly less [3H]dopamine and [14C]acetylcholine upon electrical stimulation than do slices of normotensive Wistar-Kyoto rats (WKY) at all frequencies tested. At 4 weeks similar trends were seen, but the difference in [14C]acetylcholine release was not significant. That the difference in release of dopamine was already present prior to the onset of the development of hypertension, i.e. at the age of 4 weeks, indicates that it is probably not a consequence of, but rather associated with the development of hypertension. Addition of the dopamine uptake inhibitor nomifensine to the superfusion medium caused an increase in the net release of [3H]dopamine by inhibiting re-uptake, but did not influence the difference in release between SHR and WKY. The release of labelled dopamine and acetylcholine was inhibited in the presence of the dopamine D2 receptor agonist quinpirole. The concentration-response curve for the inhibition of the release of [3H]dopamine, but not that of [14C]acetylcholine, by quinpirole was shifted to the left and the maximum inhibition was higher for SHR than for WKY. These results suggest that the difference in stimulus-evoked release of labelled dopamine in the nucleus caudatus is not the consequence of changes in the uptake mechanism of dopamine, but is associated with differences between SHR and WKY in dopamine D2 autoreceptor regulation.

Acetylcholine↗

PubMed1990

4-Aminopyridine stimulates B-50 (GAP43) phosphorylation and [3H]noradrenaline release in rat hippocampal slices.

In situ phosphorylation of the presynaptic protein kinase C substrate B-50 was investigated in rat hippocampal slices incubated with the convulsant drug 4-aminopyridine (4-AP). Phosphorylation of B-50 was significantly enhanced 1 min after the addition of 4-AP (100 microM). This increase by 4-AP was concentration dependent (estimated EC50 30-50 microM). Concomitant with the changes in B-50 phosphorylation, 4-AP also dose-dependently stimulated [3H]noradrenaline [( 3H]NA) release from the slices. 4-AP stimulated [3H]NA release within 5 min to seven times the control level. The B-50 phosphorylation induced by 4-AP remained elevated after removal of the convulsant, this is contrast to B-50 phosphorylation induced by depolarization with K+. A similar persistent increase was observed for [3H]NA release after a 5-min incubation period with 4-AP. These results give more insight into the molecular mechanisms underlying 4-AP-induced epileptogenesis and provide further evidence for the correlation between B-50 phosphorylation and neurotransmitter release in the hippocampal slice.

4-Aminopyridine↗

PubMed1989

Dopamine D-1 and D-2 receptor agonists and antagonists and neuropeptide-induced excessive grooming.

The administration of the dopamine D-1 receptor antagonist, SCH 23390, but not of the dopamine D-2 receptor antagonist, sulpiride, suppressed the excessive grooming induced by a new environment or by various neuropeptides. In addition, administration of the dopamine D-1 agonist, SK & F 38393, induced excessive grooming but that of the dopamine D-2 agonist, quinpirole, did not. It is suggested that dopamine D-1 rather than D-2 receptor stimulation is an important mechanism underlying novelty-induced as well as neuropeptide-induced excessive grooming.

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

PubMed1989

Inhibition of noradrenaline release by antibodies to B-50 (GAP-43).

Protein kinase C (PKC) is believed to have a crucial role in synaptic transmitter release and long-term potentiation. An important substrate of PKC in the brain is the neuron-specific presynaptically localized protein B-50 (also termed GAP-43, F1, pp46 or P-57). B-50 has been implicated in the regulation of polyphosphoinositide metabolism and calmodulin binding, and in the mechanisms of neurite outgrowth, long-term potentiation and transmitter release. It is still unknown, however, whether B-50 (and/or its phosphorylation) is essential to any of these processes. Here we report the results of studies in which antibodies to B-50, which interfere with B-50 phosphorylation, were introduced into rat cortical synaptosomes that were permeabilized with streptolysin-O (SL-O). We found that the release of [3H]noradrenaline, induced by increasing the Ca2+ concentration in the buffer, is inhibited completely by the antibodies. These results provide the first demonstration of a causal relationship between the PKC substrate B-50 and the release of neurotransmitter.

Animals↗

PubMed1989

ACTH-(1-24) enhances the electrically stimulated release of [3H]dopamine from rat septal slices via a dopamine D2 receptor-independent mechanism.

ACTH-(1-24) enhanced the basal as well as the electrically stimulated release of [3H]dopamine from rat septal slices in vitro. In the absence of Ca2+ from the superfusion medium the effect of ACTH-(1-24) on the electrically stimulated release of [3H]dopamine was abolished. The stimulus-evoked release of [3H]dopamine from septal slices appeared to be modulated through dopamine receptors of the D2 subtype: the dopamine D2 receptor agonists 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) and quinpirole reduced, whereas the dopamine D2 receptor antagonist sulpiride enhanced the electrically stimulated release of [3H]dopamine. The magnitude of the effect of ACTH-(1-24) on [3H]dopamine release was the same in the presence or absence of N-0437, quinpirole and sulpiride. ACTH-(1-24) had no effect on either the basal or the electrically stimulated release of [3H]noradrenaline. Also when the electrically stimulated release of [3H]noradrenaline was reduced by the alpha 2-adrenoceptor agonist clonidine, the peptide was without effect. These results show that ACTH-(1-24) selectively enhances the release of [3H]dopamine from septal slices. The effect of the peptide is independent of the degree of activation of dopamine D2 receptors which modulate the stimulus-evoked release of [3H]dopamine. These results suggest that ACTH-(1-24) enhances the stimulus-evoked release of dopamine in the septum via a mechanism not associated with dopamine D2 autoreceptors.

Adrenocorticotropic Hormone↗

PubMed1989

Phosphorylation of B-50 (GAP43) is correlated with neurotransmitter release in rat hippocampal slices.

Recent studies have demonstrated that phorbol diesters enhance the release of various neurotransmitters. It is generally accepted that activation of protein kinase C (PKC) is the mechanism by which phorbol diesters act on neurotransmitter release. The action of PKC in neurotransmitter release is very likely mediated by phosphorylation of substrate proteins localized in the presynaptic nerve terminal. An important presynaptic substrate of PKC is B-50. To investigate whether B-50 mediates the actions of PKC in neurotransmitter release, we have studied B-50 phosphorylation in intact rat hippocampal slices under conditions that stimulate or inhibit PKC and neurotransmitter release. The slices were labelled with [32P]orthophosphate. After treatment, the slices were homogenized, B-50 was immunoprecipitated from the slice homogenate, and the incorporation of 32P into B-50 was determined. Chemical depolarization (30 mM K+) and the presence of phorbol diesters, conditions that stimulate neurotransmitter release, separately and in combination, also enhance B-50 phosphorylation. Polymyxin B, an inhibitor of PKC and neurotransmitter release, decreases concentration dependently the depolarization-induced stimulation of B-50 phosphorylation. The effects of depolarization are not detectable at low extracellular Ca2+ concentrations. It is concluded that in rat hippocampal slices B-50 may mediate the action of PKC in neurotransmitter release.

Animals↗

PubMed1988

Rapid postmortem increase in extracellular dopamine in the rat brain as assessed by brain microdialysis.

Extracellular dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat nucleus accumbens were determined before and shortly following death using microdialysis. A maximal 400-fold increase in the output of DA was observed within the first 5 min of death. DA output remained elevated over the following hour at a level of approximately 70-fold above pre-death values. In contrast to that of DA, DOPAC and HVA output gradually declined. Before death the extracellular DOPAC/DA ratio was about 250; after death this ratio dropped to 0.44 at 5 min. These observations may have important implications for experiments measuring the output of (endogenous) DA and its metabolites from brain tissue in vitro: autoregulation of, e.g., transmitter release and synthesis in vitro may be seriously disrupted by the observed depletion of transmitter storage granules.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

The neuroleptic-like peptide desenkephalin-gamma-endorphin does not antagonize the dopamine receptor agonist-induced inhibition of the release of [3H]dopamine from rat nucleus accumbens slices in vitro.

In rats, the non-opioid beta-endorphin (beta E) fragment desenkephalin-gamma-endorphin (DE gamma E, beta E6-17) antagonizes the hypomotility induced by a small dose of dopamine (DA) receptor agonists. It has been suggested that DE gamma E might act in this respect by a direct or indirect blockade of presynaptically located DA receptors in the nucleus accumbens, thereby causing an increase of DA release. Therefore in the present study the effect of DE gamma E was examined on DA receptor agonist-induced inhibition of the electrically evoked release of previously accumulated [3H]DA from rat nucleus accumbens slices in vitro. The DA receptor agonists apomorphine, LY 171555 and n,n-di-n-propyl-7-hydroxy-2-aminotetralin (DP-7-AT) inhibited in a concentration-dependent manner the electrically evoked release of [3H]DA. The selective D2 receptor antagonist (-)-sulpiride blocked the effects of apomorphine, corroborating that the DA receptor involved is of a D2 type. DE gamma E was tested at several concentrations (10(-9)-10(-6) M) and under various experimental conditions. DE gamma E, by itself, did not affect either the electrically stimulated or the basal release of [3H]DA. The inhibiting effect of DA receptor agonists was slightly reduced by DE gamma E, but this effect was present in some experiments only. It is concluded that DE gamma E does not function as an antagonist for the DA receptor mediating DA release and that the interaction observed in behavioural experiments between DA agonists and DE gamma E does not occur at the level of this receptor.

Animals↗

PubMed1987

Microinjection of anti-vasopressin serum into limbic structures of the rat brain: effects on passive avoidance responding and on local catecholamine utilization.

Rats which had received bilateral microinjections of 1:50 diluted anti-vasopressin serum into the dorsal or ventral hippocampus, immediately after the learning trial of a one-trial passive avoidance test, showed a reduction in avoidance latency scores during subsequent retention tests 24 and 48 h later. Postlearning microinjection of anti-vasopressin serum into either the dorsolateral septum or the caudate nucleus was without effect on the retention of passive avoidance behavior. Microinjection of anti-vasopressin serum 1 h before the 24-h retention session into either the dorsal hippocampus, the ventral hippocampus or the dorsolateral septum attenuated avoidance responding during both the 24-h and 48-h retention sessions, whereas preretention microinjection of the serum into the caudate nucleus was not effective. Intracerebroventricular administration of the anti-vasopressin serum in amounts similar to those used in the microinjection experiments did not affect retention scores when given either immediately after the learning trial or before the first retention session. One week after the behavioral experiments, a repeated microinjection of anti-vasopressin serum decreased the local alpha-methyl-p-tyrosine methylester (alpha-MPT)-induced disappearance of noradrenaline in the ventral hippocampus and the dorsal hippocampus respectively. Microinjection of the antiserum in the dorsolateral septum enhanced noradrenaline disappearance in this brain region. No effect was found on alpha-MPT-induced dopamine disappearance in the caudate nucleus following local microinjection of anti-vasopressin serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Basal and electrically stimulated release of [3H]noradrenaline and [3H]dopamine from rat amygdala slices in vitro: effects of 4 beta-phorbol 12,13-dibutyrate, 4 alpha-phorbol 12,13-didecanoate and polymyxin B.

The protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDB) enhanced in a concentration-dependent manner the electrically stimulated release of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) from rat amygdala slices in vitro. PDB enhanced the basal release of [3H]NA and [3H]DA as well. 4 alpha-Phorbol 12,13-didecanoate, which lacks the capacity to activate protein kinase C, was without effect on either basal or electrically stimulated release of [3H]NA and [3H]DA. Polymyxin B, which is a relatively selective protein kinase C inhibitor, decreased in a concentration-dependent manner the electrically stimulated release of both [3H]NA and [3H]DA from amygdala slices, whereas it enhanced the basal release of both neuromessengers. In the presence of 1.5 X 10(-7) M PDB, a concentration which when added to the superfusion medium alone doubled the electrically stimulated release of both [3H]NA and [3H]DA, polymyxin B again decreased in a concentration-dependent manner the release of both neuromessengers. At all polymyxin B concentrations used, the effect of the PKC inhibitor, expressed as percent inhibition, in the presence of PDB was approximately the same as that observed in the absence of PDB. This suggests that the antagonism between PDB and polymyxin B at the level of protein kinase C is not a competitive one. The effects of PDB and polymyxin B on basal release were additive. Taken together, these data suggest that in the amygdala presynaptically localized protein kinase C plays a role in signal transduction processes related to the exocytotic secretion of NA and DA from their nerve terminals.

Amygdala↗