Depolarization-evoked Release Research Articles

Occurrence of two types of secretory vesicles in the human neuroblastoma SH-SY5Y.

Western blot analysis showed that the human neuroblastoma SH-SY5Y expresses the proteins synaptotagmin l, synaptobrevin, synapsin-l, rab3a, syntaxin, SNAP-25, NSF, alpha-SNAP, and munc-18, which have been implicated in the movement, docking, and fusion of vesicles during exocytosis from other neuroendocrine cells. The subcellular localization of secretogranins I and II, synaptotagmin l, neuropeptide Y, rab3a, synaptobrevin, synaptophysin, and syntaxin was investigated by immunofluorescence microscopy and revealed punctate staining patterns characteristic of secretory vesicles. The comigration of noradrenaline, secretogranin II, and dopamine-beta-hydroxylase on sucrose-D2O gradient fractions indicates the presence of a population of noradrenaline-containing large dense-cored vesicles (LDCVs). In addition, a lighter vesicle population is also present that does not appear to be noradrenergic and contains a 48-kDa synaptophysin antigen absent from the large dense-cored vesicles. Immunocytochemical experiments show that not all of the vesicles that express synaptotagmin l contain secretogranin II. Thus, our studies suggest that two types of vesicle are present in SH-SY5Y cells, one of which, the LDCVs, contains noradrenaline. These findings confirm our previous studies suggesting that depolarization-evoked release of noradrenaline from SH-SY5Y occurs by LDCV exocytosis. This enhances the value of SH-SY5Y as a cell line in which to study the mechanism by which noradrenaline release is regulated.

Inhibition by cigarette smoke of lipid peroxidation-induced neurotransmitter release

Effects of water-soluble substance in cigarette smoke on neurotransmitter release were investigated using nerve terminals (synaptosomes) prepared from rat cerebral cortex. 2,2′-Azobis (2-amidinopropane) dihydrochloride (ABAP), a peroxyl radical-generator, enhanced the depolarization-evoked release of glutamate and aspartate from synaptosomes with concomitant increase in thiobarbituric acid-reactive substances (TBA-RS) levels in membrane lipids of synaptosomes. The trapped smoke-substance attenuated the lipid peroxidation-enhanced release of excitatory amino acids during the depolarization with reduction in TBA-RS, although it failed to affect the basal release of neurotransmitters. These data suggest that cigarette smoke may possess antioxidant properties to reduce oxidation-induced enhancement of transmitter release from nerve terminals.

RECEPTORS CONTROLLING TRANSMITTER RELEASE FROM SYMPATHETIC NEURONS IN VITRO

Primary cultures of postganglionic sympathetic neurons were established more than 30 years ago. More recently, these cultures have been used to characterize various neurotransmitter receptors that govern sympathetic transmitter release. These receptors may be categorized into at least three groups: (1) receptors which evoke transmitter release; (2) receptors which facilitate; (3) receptors which inhibit, depolarization-evoked release. Group (1) comprises nicotinic and muscarinic acetylcholine receptors, P 2X purinoceptors and pyrimidinoceptors. Group (2) currently harbours β-adrenoceptors, P 2 purinoceptors, receptors for PACAP and VIP, as well as prostanoid EP 1 receptors. In group (3), muscarinic cholinoceptors, α 2- and β-adrenoceptors, P 2 purinoceptors, and receptors for the neuropeptides NPY, somatostatin (SRIF 1) and LHRH, as well as opioid (δ and κ) receptors can be found. Receptors which regulate transmitter release from neurons in cell culture may be located either at the somatodendritic region or at the sites of exocytosis, i.e. the presynaptic specializations of axons. Most of the receptors that evoke release are located at the soma. There, ionotropic receptors cause depolarizations to generate action potentials which then trigger Ca 2+-dependent exocytosis at axon terminals. The signalling mechanisms of metabotropic receptors which evoke release still remain to be identified. Receptors which facilitate depolarization-evoked release appear to be located preferentially at presynaptic sites and presumably act via an increase in cyclic AMP. Receptors which inhibit stimulation evoked release are also presynaptic origin and most commonly rely on a G protein-mediated blockade of voltage-gated Ca 2+ channels. Results obtained with primary cell cultures of postganglionic sympathetic neurons have now supplemented previous data about neurotransmitter receptors involved in the regulation of ganglionic as well as sympatho-effector transmission. In the future, this technique may prove useful to identify yet unrecognized receptors which control the output of the sympathetic nervous system and to elucidate underlying signalling mechanisms. © 1997 Elsevier Science Ltd. All Rights Reserved.

Lipid-dependent modulation of Ca2+ availability in isolated mossy fiber nerve endings.

An enhancement of glutamate release from hippocampal neurons has been implicated in long-term potentiation, which is thought to be a cellular correlate of learning and memory. This phenomenom appears to be involved the activation of protein kinase C and lipid second messengers have been implicated in this process. The purpose of this study was to examine how lipid-derived second messengers, which are known to potentiate glutamate release, influence the accumulation of intraterminal free Ca2+, since exocytosis requires Ca2+ and a potentiation of Ca2+ accumulation may provide a molecular mechanism for enhancing glutamate release. The activation of protein kinase C with phorbol esters potentiates the depolarization-evoked release of glutamate from mossy fiber and other hippocampal nerve terminals. Here we show that the activation of protein kinase C also enhances evoked presynaptic Ca2+ accumulation and this effect is attenuated by the protein kinase C inhibitor staurosporine. In addition, the protein kinase C-dependent increase in evoked Ca2+ accumulation was reduced by inhibitors of phospholipase A2 and voltage-sensitive Ca2+ channels, as well as by a lipoxygenase product of arachidonic acid metabolism. That some of the effects of protein kinase C activation were mediated through phospholipase A2 was also indicated by the ability of staurosporine to reduce the Ca2+ accumulation induced by arachidonic acid or the phospholipase A2 activator melittin. Similarly, the synergistic facilitation of evoked Ca2+ accumulation induced by a combination of arachidonic acid and diacylglycerol analogs was attenuated by staurosporine. We suggest, therefore, that the protein kinase C-dependent potentiation of evoked glutamate release is reflected by increases in presynaptic Ca2+ and that the lipid second messengers play a central role in this enhancement of chemical transmission processes.

Clinical associations and time of onset of cerebral white matter damage in very preterm babies.

Neuropathological examinations were carried out at necropsy on 83 very pre-term babies who died during their first hospital admission. Forty seven (57%) babies had evidence of cerebral damage-39 with ischaemic white matter damage. The time of onset of ischaemic lesions was thought to be prenatal in 12 cases (31%) and postnatal in a further 12 (31%). The exact timing of damage could not be determined in 15 (38%) cases. Maternal and neonatal case notes were reviewed to ascertain clinical associations of ischaemic white matter damage. There were no clear associations between adverse clinical factors and prenatal ischaemic white matter damage. In contrast, pre-eclampsia, intrauterine growth retardation, and delivery without labour were associated with postnatal damage as were neonatal sepsis, necrotising enterocolitis, and seizures. The absence of a clear association between the timing of adverse clinical factors and the timing of ischaemic cerebral damage suggests that cerebral damage in very preterm babies may result from a sequence of events rather than one specific insult.

Single-domain/bound calcium hypothesis of transmitter release and facilitation.

1. We describe a model of transmitter release that is based on the finding that release can be gated during the opening of individual Ca2+ channels, suggesting that the release site can be activated by the Ca2+ domain under a single channel. In this model each release site contains four independent Ca2+ binding sites or gates with unbinding kinetics graded from slow to fast and affinities ranging from high to low. All four gates must be bound for release to occur. Thus synaptic dynamics are governed by the kinetics of Ca2+ binding and unbinding from release sites, not Ca2+ diffusion. 2. Fast facilitation occurs when an action potential invades a terminal with one or more ions remaining bound to the release sites. Residual free Ca2+ is not necessary for facilitation with this mechanism, but if present it would enhance facilitation by binding to high-affinity gates between pulses. 3. This model can account for key features of release. These include fourth-power cooperativity with regard to external Ca2+; a release time course that is virtually independent of an increase in quantal content; an inverse relation between external Ca2+ and the degree of facilitation; and a steplike increase in facilitation with increasing stimulus frequency, with each step corresponding to a unitary decline in the Ca2+ cooperativity. 4. Facilitation of single-channel-based secretion is shown to be robust even if channel opening is stochastic. Spontaneous release of transmitter, assumed to be due in part to spontaneous Ca2+ channel openings, is shown to be elevated during and after a train of impulses. 5. An extension of the model to include multiple Ca2+ channels per release site demonstrates that one role of overlapping Ca2+ domains may be to accentuate depolarization-evoked release relative to spontaneous release.

Release of taurine and its effects on release of neurotransmitter amino acids in rat cerebral cortex.

Taurine has been postulated to function as a neurotransmitter or neuromodulator. The possibility of depolarization-evoked release of taurine from nerve terminals, and the effects of taurine on release of endogenous glutamate (Glu), aspartate (Asp), and gamma-aminobutyrate (GABA) were examined using a superfusion of crude synaptosomes prepared from rat cerebral cortex. Taurine contents in cerebral cortex and its synaptosomes were 31.7 and 25.2 nmol/mg protein, respectively. Although the basal rate of taurine release was 35.3 pmol/min/mg protein of synaptosomes (second highest releasing rate), the 2-min stimulation with KCl (30 mM) evoked only a 1.3-fold increase in release of taurine (47.3 pmol/min/mg). The increase was largely Ca(2+)-dependent. The addition of taurine to the perfusion medium significantly reduced the depolarization-evoked increases in Glu, Asp, and GABA release. The taurine-induced reduction in GABA release was attenuated by phaclofen, a GABAB antagonist, but not by bicuculline, a GABAA antagonist. However, these antagonists did not block the effects on Glu and Asp release. These data suggest that taurine may be only partly released from nerve terminals by depolarization in the cerebral cortex, but that taurine may act upon nerve terminals to regulate the release of excitatory and inhibitory amino acid transmitters.

A comparison between the stimulated and paroxysmal release of endogenous amino acids from rat cerebellar, striatal and hippocampal slices: a manifestation of spreading depression?

Spreading depression, which can be evoked by a variety of stimuli both in vitro and in vivo, is associated with profound changes in extracellular ion concentrations and enhanced release of neurotransmitter amino acids. We have observed a transient spontaneous release of amino acids in slice preparations obtained from rat cerebellum, striatum and hippocampus; this phenomenon has similar properties to stimulus-evoked spreading depression. Aspartate, glutamate, glutamine, serine, glycine and γ-aminobutyric acid (GABA) release were potentiated during these episodes in all three brain regions, with a variable effect upon taurine release. When compared to glutamate release, a consistently high release of aspartate, glycine and serine was observed. Amino acid release, evoked by whole slice depolarization using veratridine (10–25 μM) or elevated potassium (35–60 mM) consistently enhanced glutamate release, and to a lesser extent aspartate release, but had negligible effect upon the other amino acids. Thus, the release profiles for spontaneous and depolarization-evoked release are markedly different. We suggest that the spontaneous release observed in brain slices represents a spreading depression-like phenomenon; the putative roles of the amino acids are discussed.

Anesthetics affect the uptake but not the depolarization-evoked release of GABA in rat striatal synaptosomes.

Numerous classes of anesthetic agents have been shown to enhance the effects mediated by the postsynaptic gamma-aminobutyric acid A (GABAA) receptor-coupled chloride channel in the mammalian central nervous system. However, presynaptic actions of anesthetics potentially relevant to clinical anesthesia remain to be clarified. Therefore, in this study, the effects of intravenous and volatile anesthetics on both the uptake and the depolarization-evoked release of GABA in the rat striatum were investigated. Assay for specific GABA uptake was performed by measuring the radioactivity incorporated in purified striatal synaptosomes incubated with 3H-GABA (20 nM, 5 min, 37 degrees C) and increasing concentrations of anesthetics in either the presence or the absence of nipecotic acid (1 mM, a specific GABA uptake inhibitor). Assay for GABA release consisted of superfusing 3H-GABA preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml.min-1, 37 degrees C) and measuring the radioactivity obtained from 0.5 ml fractions over 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of either KCl alone (9 mM, 15 mM) or with various concentrations of anesthetics (5 min), and finally, with no pharmacologic stimulation (5 min). The following anesthetic agents were tested: propofol, etomidate, thiopental, ketamine, halothane, enflurane, isoflurane, and clonidine. More than 95% of 3H-GABA uptake was blocked by a 10(-3)-M concentration of nipecotic acid. Propofol, etomidate, thiopental, and ketamine induced a dose-related, reversible, noncompetitive, inhibition of 3H-GABA uptake: IC50 = 4.6 +/- 0.3 x 10(-5) M, 5.8 +/- 0.3 x 10(-5) M, 2.1 +/- 0.4 x 10(-3) M, and 4.9 +/- 0.5 x 10(-4) M for propofol, etomidate, thiopental, and ketamine, respectively. Volatile agents and clonidine had no significant effect, even when used at concentrations greater than those used clinically. KCl application induced a significant, calcium-dependent, concentration-related, increase from basal 3H-GABA release, +34 +/- 10% (P < 0.01) and +61 +/- 13% (P < 0.001), respectively, for 9 mM and 15 mM KCl. The release of 3H-GABA elicited by KCl was not affected by any of the anesthetic agents tested. These results indicate that most of the intravenous but not the volatile anesthetics inhibit the specific high-affinity 3H-GABA uptake process in vitro in striatal nerve terminals. However, this action was observed at clinically relevant concentrations only for propofol and etomidate. In contrast, the depolarization-evoked 3H-GABA release was not affected by anesthetics. Together, these data suggest that inhibition of GABA uptake, which results in synaptic GABA accumulation, might contribute to propofol and etomidate anesthesia.

Short-term modulation of glutamatergic synapses in adult rat hippocampus by NGF.

Nerve growth factor promotes survival and differentiation of selected groups of neurones through long-term adaptive changes in cell function. While production of this neurotrophin in target cells in hippocampus is regulated in part by afferent glutamate neuronal input, we report now for the first time that nerve growth factor has a direct potentiating effect on spontaneous and depolarization-evoked release of glutamate from hippocampal nerve endings, accompanied by an increase in the excitatory postsynaptic potential of CA1 neurones. This correlated with increased incorporation of [32P]phosphate into synapsin I. Reciprocal positive feedback between production of trophic factors in target cells by neurotransmitter released from afferent neuronal inputs and the modulation of presynaptic neurotransmitter release by target-derived trophic factors provides a novel mechanism for short-term control over synaptic communication.

Glutamate and N-methyl-D-aspartate affect release from crayfish axon terminals in a voltage-dependent manner.

In the crayfish neuromuscular junction, the excitatory transmitter is glutamate. The present study shows that at concentrations as low as 5 x 10(-7) M, glutamate affects the depolarization-evoked release of neurotransmitter. Furthermore, the effect of glutamate on release is voltage-dependent and depends on the level of the depolarizing pulse. Nerve terminals were exposed to 5 x 10(-7) M tetrodotoxin and then depolarized to different levels by a macropatch electrode. Depending on the amplitude of the depolarizing pulse, glutamate (5 x 10(-7) to 1 x 10(-5) M) had a dual effect on release. At small depolarizing pulses, glutamate reduced release, whereas at large depolarizing pulses, it enhanced it. Glutamate at 10(-6) M had no significant effect on action-potential-induced release. At 10(-4) M glutamate, the action-potential-induced release was always inhibited. N-Methyl-D-aspartate was found to mimic one of the effects of glutamate: N-methyl-D-aspartate (10(-7) to 10(-5) M) reduced release at small depolarizing pulses but had no effect with larger depolarizations. 2-Amino-5-phosphonovaleric acid blocked the effect of N-methyl-D-aspartate.

Comparison of the superfused efflux of preaccumulated d-[ 3H]aspartate and endogenous l-aspartate and l-glutamate from rat cerebrocortical minislices

Because the validity of the use of preaccumulated isotopic excitatory amino acids (EAAs) to index the depolarization-evoked release of endogenous EAAs has been questioned, we compared the K +-evoked efflux of preaccumulated d-[ 3H]aspartate from rat cerebrocortical minislices with that of endogenous l-aspartate and l-glutamate. Release of all EAAs increased with the rate of superfusion. Using the most rapid rate (1.6 ml/min), transient elevations in [K +] caused a concentration-dependent increase, with 50 mM K + evoking a 33-, 23- and 93-fold increase in the efflux of d-[ 3H]aspartate, l-aspartate and l-glutamate, respectively; this efflux was Ca 2+-dependent and tetrodotoxin insensitive. Under polarized conditions (5 mM K +), 1 mM kainic acid increased the efflux of preaccumulated and endogenous EAAs. These elevations were not blocked by the competitive kainate receptor antagonist 6,7-dinitroquinoxaline-2–3-dione (DNQX) and were not affected by removing Ca 2+ ions. We conclude that in superfused cortical minislices, the efflux of preaccumulated d-[ 3H]aspartate provides a robust and reliable index of the release of endogenous l-aspartate and l-glutamate.

On the Role of Enkephalin Cotransmission in the GABAergic Striatal Efferents to the Globus Pallidus

In the MPTP-treated primate model of Parkinson's disease, loss of dopaminergic afferents to the striatum leads to increased activity in striatal efferents to the external segment of the globus pallidus. This pathway utilizes both GABA and enkephalin as cotransmitters. Little is known regarding either the role of this cotransmission in the generation of parkinsonian symptoms or of the nature of any functional interaction between GABA and enkephalin. We have investigated the roles played by enkephalin and GABA in mediating parkinsonian symptoms by injection the GABAA antagonist bicuculline and the broad spectrum opioid antagonist naloxone directly into the globus pallidus in the reserpine-treated rat model of parkinsonism. Injections of bicuculline, but not naloxone, had marked antiparkinsonian effects. However, naloxone attenuated the antiparkinsonian effects of bicuculline. We interpret these findings as suggesting that increased GABAergic transmission in the globus pallidus is responsible for the generation of parkinsonian symptoms in the reserpine-treated rat. However, overactive enkephalinergic transmission is not responsible for the generation of symptoms and appears to act to reduce the effects of increased GABAergic transmission. In complementary studies in vitro, we have demonstrated a potential mechanism for this negative interaction. Met-enkephalin (3-10 μM) reduced depolarization-evoked release of GABA from terminals in slices prepared from rat globus pallidus (IC50, 0.38 μM). A better comprehension of the mechanisms by which enkephalin and other peptides modulate the action of amino acid transmitters in the basal ganglia is critical to the understanding of the neural processes underlying basal ganglia function and movement disorders.

Functional Evidence for Retinal Adenosine Receptors

Adenosine is a potent modulator of various physiological functions. Although adenosine receptors have been demonstrated in the retina, little is known about their functional role. This study determined the effects of relatively selective adenosine agonists on K+ depolarization-induced release of dopamine and retinal arteriolar tone. For dopamine release studies, bovine retinas were isolated and endogenous synaptosomal stores were loaded with [3H] dopamine. Retinas were then transferred to a superfusion chamber and the spontaneous and K+ depolarization-induced release of dopamine were determined. Cyclopentyladenosine (CPA) did not significantly alter the spontaneous release of dopamine; however, CPA produced a dose-related inhibition of K+ depolarization-evoked release of dopamine. This CPA-induced suppression of dopamine release was reversed by pretreatment with the adenosine A1 antagonist cyclopentyltheophylline. In retinal vasculature studies, adenosine and its agonists injected intravitreally dilated retinal arterioles and venules, in newborn pigs, with a potency profile indicative of mediation by A2 adenosine receptors. Intravitreal injections of drugs inhibiting the metabolism of endogenous adenosine also induced an arteriolar vasodilation which was inhibited by co-administration of an adenosine receptor antagonist. Intravitreally administered adenosine antagonists also attenuated the vasodilative response to both systemic hypoxia and systemic hypotension in the newborn pig, indicating that endogenously produced adenosine is important in retinal blood flow regulation.

Effects of taurine on depolarization-evoked release of amino acids from rat cortical synaptosomes

Effects of taurine on endogenous aspartic acid (Asp), glutamic acid (Glu) and γ-aminobutyric acid (GABA) release has been investigated using synaptosomes prepared from rat cerebral cortex. Although basal release of these amino acids was not affected, taurine inhibited KCl (30 mM)-evoked overflow of Asp, Glu and GABA in a concentration-dependent manner with potencies (IC 50) of 1 μM, 0.8 μM and 5 nM, respectively. Taurine (10 μM) maximally inhibited K +-evoked Asp, Glu and GABA overflow by 28, 37 and 65%, respectively. Phaclofen (10 μM, a GABA B receptor antagonist), but not bicuculline (10 μM, a GABA A receptor antagonist), counteracted the inhibition of GABA overflow, although the inhibition of Asp and Glu overflow was not attenuated. These data suggest that taurine may inhibit GABA release through the activation of presynaptic GABA B autoreceptors and, at high concentration, also act on Asp- and Glu-nerve terminals to regulate release of excitatory amino acids in rat cortex.

Involvement of calcium channels in depolarization-evoked release of adenosine from spinal cord synaptosomes.

The potential involvement of L- and N-type voltage-sensitive calcium (Ca2+) channels and a voltage-independent receptor-operated Ca2+ channel in the release of adenosine from dorsal spinal cord synaptosomes induced by depolarization with K+ and capsaicin was examined. Bay K 8644 (10 nM) augmented release of adenosine in the presence of a partial depolarization with K+ (addition of 6 mM) but not capsaicin (1 and 10 microM). This augmentation was dose dependent from 1 to 10 nM and was followed by inhibition of release from 30 to 100 nM. Nifedipine and nitrendipine inhibited the augmenting effect of Bay K 8644 in a dose-dependent manner, but neither antagonist had any effect on release of adenosine produced by K+ (24 mM) or capsaicin (1 and 10 microM). omega-Conotoxin inhibited K(+)-evoked release of adenosine in a dose-dependent manner but had no effect on capsaicin-evoked release. Ruthenium red blocked capsaicin-induced release of adenosine but had no effect on K(+)-evoked release. Although L-type voltage-sensitive Ca2+ channels can modulate release of adenosine when synaptosomes are partially depolarized with K+, N-type voltage-sensitive Ca2+ channels are primarily involved in K(+)-evoked release of adenosine. Capsaicin-evoked release of adenosine does not involve either L- or N-type Ca2+ channels, but is dependent on a mechanism that is sensitive to ruthenium red.

Differential involvement of protein kinase C in transmitter release and response to excitatory amino acids in cultured cerebellar neurons

Cerebellar granule cells cultured in the presence of a differentiating factor isolated from rabbit serum exhibit, at variance with those cultured in fetal calf serum, an almost complete resistance to excitatory aminoacid (EAA)-induced cytotoxicity. We investigated the behaviour of protein kinase C (PKC), strongly implicated in EAA cytotoxicity, in the two types of culture. Phorbol esters, used to monitor the enzyme, enhanced the depolarization-evoked release of D-[3H]aspartate, but less effectively in factor-conditioned cells. EAAs increased phorbol esters binding in both cultures, but the effect was briefly lasting in factor-conditioned cells. The different behaviour of PKC is postulated to be causally related to different response to EAA of the cultures.

Release of endogenous glutamic and aspartic acids from cerebrocortex synaptosomes and its modulation through activation of a γ-aminobutyric acid B (GABA B) receptor subtype

The depolarization-evoked release of endogenous glutamate (GLU) and -aspartate (ASP) and its modulation mediated by γ-aminobutyric acid (GABA) heteroreceptors was investigated in superfused rat cerebrocortical synaptosomes. Exposure to 12 mM K + enhanced the release of GLU and ASP. The K +-evoked overflow of both amino acids was largely Ca 2+-dependent. Exogenous GABA inhibited the K +-evoked overflow of GLU (EC 50 2.8 μM) and ASP (EC 50 2.7 μM). The effect of GABA was mimicked by the GABA B receptor agonist (−)-baclofen (EC 50 2.0 μM for GLU and 1.3 μM for ASP release) but not by the GABA A receptor agonist muscimol, up to 100 μM. Accordingly, the GABA-induced inhibition of GLU and ASP release was not affected by the GABA A receptor antagonists, bicuculline or picrotoxin, but was antagonized by the GABA B receptor antagonist, 3-amino-propyl(diethoxymethyl)phosphinic acid (CGP 35348). The GABA effect was, however, insensitive to another GABA B receptor antagonist, phaclofen, up to 1,000 μM. It can be concluded that GABA heteroreceptors of the GABA B type regulating the depolarization-evoked release of GLU and ASP are present on cortical GLU/ASP-releasing nerve terminals. These receptors may be classified as a phaclofen-insensitive GABA B receptor subtype.

1205 Depolarization-evoked acetylcholine release from cultured rat septal neurons is induced by nerve growth factor but not by dibutyryl cyclic AMP treatment

1205 Depolarization-evoked acetylcholine release from cultured rat septal neurons is induced by nerve growth factor but not by dibutyryl cyclic AMP treatment

Region-specific inhibition of potassium-evoked [ 3H]noradrenaline release from rat brain synaptosomes by neuropeptide Y-(13–36). Involvement of NPY receptors of the Y 2 type

The effects of the Y 2 receptor agonist neuropeptide Y NPY-(13–36) on the depolarization-evoked release of [ 3H]noradrenaline (NA) from synaptosomal preparations of the medulla oblongata, the hypothalamus, the hippocampal formation and the parieto-occipital cortex of the male rat were studied. NPY-(13–36)(0.1–100 nM) caused a concentration-related inhibition of the depolarization-induced release of [ 3H]NA in all areas studied, except the parieto-occipital cortex and inhibit depolarization-evoked [ 3H]NA release.