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PubMed1994

Neurotransmitters in subcortical somatosensory pathways.

Investigations during recent years indicate that many different neuroactive substances are involved in the transmission and modulation of somesthetic information in the central nervous system. This review surveys recent developments within the field of somatosensory neurotransmission, emphasizing immunocytochemical findings. Increasing evidence indicates a widespread role for glutamate as a fast-acting excitatory neurotransmitter at different levels in somatosensory pathways. Several studies have substantiated a role for glutamate as a neurotransmitter in primary afferent neurons and in corticofugal projections, and also indicate a neurotransmitter role for glutamate in ascending somatosensory pathways. Other substances likely to be involved in somatosensory neurotransmission include the neuropeptides. Many different peptides have been detected in primary afferent neurons with unmyelinated or thinly myelinated axons, and are thus likely to be directly involved in primary afferent neurotransmission. Some neurons giving rise to ascending somatosensory pathways, primarily those with cell bodies in the dorsal horn, are also immunoreactive for peptides. Recent investigations have shown that the expression of neuropeptides, both in primary afferent and ascending tract neurons, may change as a result of various kinds of peripheral manipulation. The occurrence of neurotransmitters in intrinsic neurons and neurons providing modulating inputs to somatosensory relay nuclei (the dorsal horn, the lateral cervical nucleus, the dorsal column nuclei and the ventrobasal thalamus) is also reviewed. Neurotransmitters and modulators in such neurons include acetylcholine, monoamines, GABA, glycine, glutamate, and various neuropeptides.

Afferent Pathways↗
PubMed1992

Compartmentalization of monoaminergic synaptic vesicles in the storage and release of neurotransmitter.

Monoaminergic nerves are characterized by the presence of a population of small synaptic vesicles (40-60 nm in diameter) containing a few large vesicles (80-90 nm in diameter). Thus, although both types of vesicles contain monoamines, the small vesicles must be considered as the organoid responsible for the storage and release of the neurotransmitter, whereas the large ones possibly are involved in the modulation of the process. The small vesicles are electron-lucent or have an osmiophilic electron-dense core that is always linked to the vesicle membrane. Considering morphological and histochemical evidence under different experimental conditions, we proposed the existence of two compartments in the small vesicles: the core and the matrix, corresponding respectively to the electron-dense core and the electron-lucent space between the core and the vesicle membrane in osmium tetroxide fixations. The sizes of both compartments are inversely related, i.e., the smaller the core, the larger the matrix and vice versa. The core even disappears, giving way to a small electron-lucent vesicle made exclusively by the matrix. Thus, the matrix is a constant component of the vesicle, whereas the core is a transient one. Each compartment has a different pool of amine: a loosely bound, easily releasable pool in the matrix and a tightly bound, more resistant pool in the core. These two pools subserve, respectively, a tonic or phasic release of the neurotransmitter, correlated with a tonic or phasic stimulation of the receptor. The core may be considered as a storage or reserve pool. Experimental evidence from our laboratory supports the concept that different mechanisms are operative in both compartments in the release of the neurotransmitter. For instance, a Ca2(+)-independent release would be primarily concerned with the neurotransmitter contained in the matrix, and a Ca2(+)-dependent efflux would be primarily related with the neurotransmitter stored in the core. However, it still must be established that a simple relationship exists between each kind of stimulus and each vesicle compartment, rather than both compartments being integrated in a dynamic functional unit.

Animals↗
PubMed2002

Neurotransmitters are regulators for the migration of tumor cells and leukocytes.

Neurotransmitters are signal substances that have traditionally been regarded as mere mediators of signal states between cells in the nervous system. Whereas the mechanisms of this "classic" neurotransmitter regulation are well understood, only recently has new evidence come to light elucidating the modulatory role of neurotransmitters in immune function, and in the regulation of migration of leukocytes and tumor cells. The migration of leukocytes is, among other things, of primary importance for an anti-tumor immune response, whereas the migration of tumor cells is a prerequisite for invasion and the development of metastases. We here clarify and consolidate the latest tumor biological findings on the role of these neurotransmitters, which bind to serpentine receptors, and which are involved in leukocyte migration, tumor growth, invasion and metastasis. This review thus accentuates the complex, interactive involvement of neurotransmitters in the regulation of migration of both leukocytes and tumor cells.

Animals↗
PubMed2001

Neurotransmitters as early signals for central nervous system development.

During brain ontogenesis, the temporal and spatial generation of the different types of neuronal and glial cells from precursors occurs as a sequence of successive progenitor stages whose proliferation, survival and cell-fate choice are controlled by environmental and cellular regulatory molecules. Neurotransmitters belong to the chemical microenvironment of neural cells, even at the earliest stages of brain development. It is now established that specific neurotransmitter receptors are present on progenitor cells of the developing central nervous system and could play, during neural development, a role that has remained unsuspected until recently. The present review focuses on the occurrence of neurotransmitters and their corresponding ligand-gated ion channel receptors in immature cells, including neural stem cells of specific embryonic and neonatal brain regions. We summarize in vitro and in vivo data arguing that neurotransmitters could regulate morphogenetic events such as proliferation, growth, migration, differentiation and survival of neural precursor cells. The understanding of neurotransmitter function during early neural maturation could lead to the development of pharmacological tools aimed at improving adult brain repair strategies.

Acetylcholine↗
PubMed2005

Locally administered low nicotine-induced neurotransmitter changes in areas of cognitive function.

The present study examined the effect of a low-dose of nicotine; below that one expects to be achieved from a single cigarette, on brain regional heterogeneity and sensitivity of catecholaminergic responses. 1 microM nicotine was infused into six brain areas via a microdialysis probe: the dorsal and ventral hippocampus, the medial temporal and prefrontal cortex, the basolateral amygdala, and the ventral tegmental area (VTA). The nicotine concentration in the brain tissue near the probe site was approximately 0.1 microM. Nicotine-induced increases and decreases could be noted in dopamine (DA), norepinephrine (NE), and serotonin (5HT) levels. In particular, DA and 5HT decreased in both hippocampal areas, while NE increased in the dorsal and decreased in the ventral hippocampus. In the cortical areas, DA and NE increased and 5HT was not significantly altered. In the amygdala all three neurotransmitters increased and in the VTA, all three decreased. Many of the nicotine-induced changes in neurotransmitter concentrations were reversed in the presence of atropine. Where nicotine induced decreases in DA and 5HT in the VTA, increases were observed in the presence of atropine. A similar reversal was seen with NE in the VTA and ventral hippocampus. In contrast, the increases in DA observed in the cortex and amygdala and the increases in NE observed in the cortex, amygdala and dorsal hippocampus were inhibited by the presence of atropine. 5HT was also significantly decreased in the amygdala and both cortical areas in the presence of atropine, where nicotine alone had no significant effect. We conclude, that at low doses, nicotine significantly alters the release of DA, NE, and 5HT--in some areas increasing, in others decreasing endogenous neurotransmitter levels. This data, in conjunction with previous experiments, indicates that the effects of nicotine are regionally heterogeneous and arise from both direct and indirect actions on various receptors and neurotransmitter systems and nicotine's effects at low doses differ from that at higher doses. The changes in effects in the presence of atropine suggest that muscarinic acetylcholine receptors play a major role in nicotine's actions on neurotransmitter systems.

Animals↗
PubMed1989

Drug effects on active immobility responses: what they tell us about neurotransmitter systems and motor functions.

The literature reviewed indicates that active immobility can be promoted by systemic injections of various neurotransmitter systems, as follows: (1) Dopaminergic blockade of both D1 and D2 receptor subtypes. (2) Cholinergic agonism of both muscarinic and nicotinic receptors. (3) Noradrenergic agonism of both alpha-1 and alpha-2 receptors (but these agonists may interfere with haloperidol- and reserpine-induced catalepsy). (4) GABA agonism. (5) Histamine agonism, particularly at the H1 receptor. (6) Opiate agonism, including action of many endogenous opiate peptides, particularly those affecting mu and delta receptors. (7) Agonism by certain other peptides (neurotensin, cholecystokinin). Among the major interactions of neurotransmitter systems that regulate immobility, are the following: (1) Cholinergic-dopaminergic (cholinolytics disrupt catalepsy of dopaminergic blockade and dopaminergic agonists tend to disrupt cholinomimetic catalepsy). (2) Opiate-induced catalepsy is antagonized by the dopamine agonist, apomorphine, but is enhanced by amphetamine. It is also antagonized by certain alpha-2 adrenergic agonists, while it does not seem to be antagonized by anticholinergics. (3) Numerous other interactions have been reported, involving opiates and MSH, serotonin and dopamine mimetics, serotonin and ketamine, GABA and neuroleptics, neurotensin and anticholinergics and histamine. The significance of the multiple neurotransmitter systems is unknown. One possible explanation is that the various neurotransmitter systems participate in mediating the sensory inputs that are involved in triggering immobility and regulate the higher-order limbic and basal ganglia processing reactions that engage a final motor output pathway from the brainstem. The brain is assumed to contain two sets of systems, each with its own, or possibly overlapping, set of neurotransmitter systems, that promote either active immobility or locomotion. The systems reciprocally inhibit each other. Another view, not mutually exclusive, is that output from the locomotor-promoting system provides a negative feedback, via the active immobility pathways, to act as a "brake" on movement, while at the same time maintaining the muscular tonus that is characteristic of active immobility.

Animals↗
PubMed1995

Involvement of P-type calcium channels in high potassium-elicited release of neurotransmitters from rat brain slices.

Several types of voltage-dependent calcium channels appear to occur in neurons, although coupling of the particular subtype of calcium channels to the release of neurotransmitter has not been clearly understood. We have examined the effects of subtype-specific inhibitors of the calcium channels on depolarization-induced release of endogenous neurotransmitters from brain slices. High potassium-induced release of glutamate and aspartate from hippocampal and striatal slices was almost completely inhibited by a P-type channel blocker, omega-agatoxin IVA. omega-Agatoxin IVA also completely inhibited the release of serotonin from the hippocampal slices with almost the same potency as in the case of glutamate, whereas the potency in blocking the release of serotonin and dopamine from striatal slices was lower than that from the hippocampal slices. Another calcium channel blocker, omega-agatoxin TK, that was recently found to block P-type channels with very similar selectivity and potency to omega-agatoxin IVA, also inhibited the release of amino acid transmitters and monoamines, though its potency was lower than that of omega-agatoxin IVA. An N-type channel blocker, omega-conotoxin GVIA, partially inhibited the neurotransmitter release, but an L-type channel blocker, nifedipine was ineffective. We propose that the activation of P-type calcium channels makes a major contribution to depolarization-elicited neurotransmitter release in the CNS and that multiple P-type channels sensitive to omega-agatoxin IVA and omega-agatoxin TK modulate the neurotransmitter release.

Analysis of Variance↗
PubMed1988

Low- and high-voltage-activated calcium currents: their relationship to the site of neurotransmitter release in an identified neuron of Helisoma.

In this study we have characterized two types of Ca2+ currents in identified neuron B5 of Helisoma and have examined the relationship between these currents and neurotransmitter release. Neuron B5 contains low-voltage-activated (LVA) and high-voltage-activated (HVA) Ca2+ currents. These currents have distinct electrophysiological and pharmacological properties. To gain access to the site of neurotransmitter release, we used a model system in which somata that do not extend neurites assume the role of neurotransmitter release. Before somata gain the ability to release neurotransmitter, they contain LVA and HVA Ca2+ currents. After 3 days of culture, when spherical somata have gained the secretory capacity, only the HVA Ca2+ current is present. Experiments were also performed when neurite extension was permitted. These data indicate that neurons with processes have a differential distribution of Ca2+ currents. The soma, which does not release neurotransmitter, contains both LVA and HVA Ca2+ currents, while distal secretory processes contain only HVA current.

Animals↗
PubMed2006

Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway.

Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), has been extensively used in traditional oriental medicine for the prevention and treatment of aging-related disorders for over 2000 years. Accumulating evidence suggests that ginsenosides such as Rg1 and Rb1, which are the pharmacologically active ingredients of ginseng, modulate neurotransmission. Synapsins are abundant phosphoproteins essential for regulating neurotransmitter release. All synapsins contain a short amino-terminal domain A that is highly conserved and phosphorylated by cAMP-dependent protein kinase (PKA), which plays a key role in regulating neurotransmitter release. In the present study, we demonstrated that both Rg1 and Rb1 increased neurotransmitter release in undifferentiated and differentiated PC12 cells. However, in the presence of the PKA inhibitor H89, Rg1, but not Rb1, still induced neurotransmitter release. Moreover, Rb1, but not Rg1, enhanced the phosphorylation of synapsins via PKA pathway. In summary, Rb1 promotes neurotransmitter release by increasing the phosphorylation of synapsins through the PKA pathway, whereas the similar effects observed with Rg1 are independent of the phosphorylation of synapsins.

Animals↗
PubMed2005

Changes in cerebral neurotransmitters and metabolites induced by acute donepezil and memantine administrations: a microdialysis study.

Cholinesterase inhibitors including donepezil, rivastigmine, and galantamine and the N-methyl-D-aspartate (NMDA) antagonist, memantine are the medications currently approved for the treatment of Alzheimer's disease (AD). In addition to their beneficial effects on cognitive and functional domains typically disrupted in AD, these agents have also been shown to slow down the emergence of behavioral and psychotic symptoms associated with this disease. However, the underlying mechanisms for these therapeutic effects remain poorly understood and could involve effects of these medications on non-cholinergic or non-glutamatergic neurotransmitter systems respectively. These considerations prompted us to initiate a series of investigations to examine the acute and chronic effects of donepezil (Aricept (+/-)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-1 hydrochloride and memantine (1-amino-3,5-dimethyladamantane hydrochloride C12H21N.HCl)). The present study focuses on the acute effects of donepezil and memantine on brain extracellular levels of acetylcholine, dopamine, serotonin, norepinephrine and their metabolites. We assayed changes in the ventral and dorsal hippocampus and the prefrontal and medial temporal cortex by microdialysis. Memantine resulted in significant increases in extracellular dopamine (DA), norepinephrine (NE), and their metabolites, in the cortical regions, and in a reduction of DA in the hippocampus. Donepezil produced an increase in extracellular DA in the cortex and in the dorsal hippocampus. Norepinephrine increased in the cortex; with donepezil it increased in the dorsal hippocampus and the medial temporal cortex, and decreased in the ventral hippocampus. Interestingly both compounds decreased extracellular serotonin (5HT) levels. The metabolites of the neurotransmitters were increased in most areas. We also found an increase in extracellular acetylcholine (ACh) by memantine in the nucleus accumbens and the ventral tegmental area. Our results suggest both region and drug specific neurotransmitter effects of these agents as well as some similarities. We conclude that drugs influencing cognitive mechanisms induce changes in a number of neurotransmitters with the changes being both region and drug specific. Release and metabolism are altered and extracellular neurotransmitter levels can be increased or decreased by the drugs. Other studies are in progress to determine the pharmacological effects associated with chronic treatment with these compounds, which may be more pertinent to the clinical situation in which patients take these medications for months or years.

Acetylcholine↗
PubMed2005

Differences in the in vivo dynamics of neurotransmitter release and serotonin uptake after acute para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine revealed by chronoamperometry.

Illicit use of p-methoxyamphetamine (PMA) is rapidly increasing. However, little is known about the acute effects of PMA on neurotransmission in vivo. High-speed chronoamperometry was used to monitor neurotransmitter release and clearance in anesthetized rats after local application of PMA or 3,4-methylenedioxymethamphetamine (MDMA). In striatum, PMA caused less neurotransmitter release than MDMA. PMA-evoked release could be partially blocked by pre-treatment with a serotonin (5-HT) reuptake inhibitor, suggesting that evoked 5-HT release contributed to the electrochemical signal and was mediated by the 5-HT transporter (SERT). MDMA-evoked release was not blocked by a SERT inhibitor, suggesting that primarily DA was released. To study the effect of these amphetamines on clearance of 5-HT mediated specifically by the SERT, clearance of exogenously applied 5-HT was measured in the CA3 region of the hippocampus. In contrast to the striatum where 5-HT is cleared by both the SERT and the dopamine transporter (DAT), 5-HT is cleared primarily by the SERT in the CA3 region. This is also a region where neither PMA nor MDMA evoked release of neurotransmitter. The maximal inhibition of 5-HT clearance was greater after PMA than MDMA. These data demonstrate in vivo (1) brain region variability in the ability of PMA and MDMA to evoke release of neurotransmitter; (2) that clearance of 5-HT in the striatum is mediated by both the SERT and the DAT; (3) distinct differences in the amount and nature of neurotransmitter released in the striatum after local application of PMA and MDMA and (4) that PMA is a more efficacious inhibitor of 5-HT clearance in the hippocampus than MDMA. These fundamental differences may account for the more severe adverse reactions seen clinically after PMA, compared to MDMA.

Amphetamines↗
PubMed2006

Neurotransmitter inactivation is important for the origin of nerve system in animal early evolution: a suggestion from genomic comparison.

Metazoans possess complicated multicellular structure among the multicellularities of eukaryotes. One evolutionary pressure that permits such complexity relates to the directed and precise informational transmission performed by numerous synapses in neuron system. Neurotransmitter inactivations play essential roles in the termination of synaptic transmission and are thus crucial for precise synaptic transmission. Here, we performed a genomic comparison among 11 eukaryotic organisms including five bilaterian species and six pan-unicellular eukaryotes to search for genes related to metazoan multicellular function. The result showed that the majority of genes related to neurotransmitter inactivation in the synaptic cleft endured high and stable selective pressure and were specifically present in bilaterians, whereas genes related to transmitter release and postsynaptic transmitter receptors did not show these properties. From these data we conclude that neurotransmitter inaction may play a critical role in the origin of the nerve system encountered in the early evolution of metazoan. In addition, we suggest that neurotransmitter inactivation probably participates in the formation or refinement of the synapse, following the concept of "ontogeny recapitulates phylogeny." Further experimental evidence is needed to support the suggestion and to explain the importance of neurotransmitter inactivation to metazoan multicellular function.

Animals↗
PubMed1991

The pre- and postnatal influence of hormones and neurotransmitters on sexual differentiation of the mammalian hypothalamus.

A number of brain structures and a great number of brain functions have been shown to be sexually dimorphic. It has also been shown that development and differentiation of these structures and functions proceeds during a critical pre- and postnatal period of increased susceptibility, and is controlled by gonadal steroids and neurotransmitter substances. The brain of male and female mammals seems to be still undifferentiated before the period of increased susceptibility to gonadal steroids and neurotransmitters starts. Feminization of brain structure and functions, e.g., establishment of the cyclic LH-surge mechanism and the expression of lordosis behavior, seems to depend on the moderate interaction of estrogens with the developing nervous system. Defeminization and masculinization of brain functions seem to be established during interaction of the developing nervous system with androgens, which have to be converted, at least in part, into estrogens. Structural differentiation of the male brain, e.g., the sexually dimorphic nucleus of the preoptic area (SDN-POA), seems to be exclusively estrogen-dependent, during differentiation of male brain functions, however, estrogens may be supportive, rather than directive, to the primary action of androgens. The molecular mechanisms of sexual differentiation of the brain are not yet fully understood. It seems, however, that the priming action of gonadal steroids during the period of increased susceptibility is either mediated by neurotransmitters, or neurotransmitters modulate the priming action of gonadal steroids. In particular, the adrenergic, the serotoninergic, the cholinergic, and possibly the dopaminergic system were shown to have strong influences on sexual differentiation of brain structure and functions. In contrast to the great number of available studies on the influence of gonadal steroids on sexual differentiation of the brain, there are rather few studies available concerning the influence of neurotransmitter systems. The available results are partly contradictory, so that an interpretation must be done with caution and will leave plenty of room for speculation. Postnatal application of compounds which stimulate or inhibit adrenergic activity mainly affected the neural control of gonadotropin secretion, and had only minor influences on differentiation of behavior patterns. It seems, however, that adrenergic participation in the differentiation of the center for cyclic gonadotropin release is very complex and stimulatory and inhibitory components may operate simultaneously. Activation or inhibition of beta-adrenergic receptors during postnatal development was shown to impair the responsiveness of the center for cyclic gonadotropin release to gonadal steroids, and impairs the expression of ejaculatory behavior in male rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

Chronic and acute regulation of Na+/Cl- -dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems.

Na+/Cl- -dependent neurotransmitter transporters, which constitute a gene superfamily, are crucial for limiting neurotransmitter activity. Thus, it is critical to understand their regulation. This review focuses primarily on the norepinephrine transporter, the dopamine transporter, the serotonin transporter, and the gamma-aminobutyric acid transporter GAT1. Chronic administration of drugs that alter neurotransmitter release or inhibit transporter activity can produce persistent compensatory changes in brain transporter number and activity. However, regulation has not been universally observed. Transient alterations in norepinephrine transporter, dopamine transporter, serotonin transporter, and GAT1 function and/or number occur in response to more acute manipulations, including membrane potential changes, substrate exposure, ethanol exposure, and presynaptic receptor activation/inhibition. In many cases, acute regulation has been shown to result from a rapid redistribution of the transporter between the cell surface and intracellular sites. Second messenger systems involved in this rapid regulation include protein kinases and phosphatases, of which protein kinase C has been the best characterized. These signaling systems share the common characteristic of altering maximal transport velocity and/or cell surface expression, consistent with regulation of transporter trafficking. Although less well characterized, arachidonic acid, reactive oxygen species, and nitric oxide also alter transporter function. In addition to post-translational modifications, cytoskeleton interactions and transporter oligomerization regulate transporter activity and trafficking. Furthermore, promoter regions involved in transporter transcriptional regulation have begun to be identified. Together, these findings suggest that Na+/Cl- -dependent neurotransmitter transporters are regulated both long-term and in a more dynamic manner, thereby providing several distinct mechanisms for altering synaptic neurotransmitter concentrations and neurotransmission.

Animals↗
PubMed2003

Modification of the dopaminergic neurotransmitters in striatum, frontal cortex and hippocampus of rats fed for 21 months with trans isomers of alpha-linolenic acid.

Deficiency in n-3 fatty acids is known to disturb the release of dopaminergic neurotransmitters in rat brain. Since isomerization reduces the bioavailability of dietary fatty acids, the effect of the conversion of alpha-linolenic acid into trans alpha-linolenic acid on the dopaminergic neurotransmission was studied. Rats were fed for 21 months with a control diet, a diet unbalanced in cis alpha-linolenic acid and containing trans alpha-linolenic acid or the same diet in which the imbalance was corrected by increasing the levels of cis alpha-linolenic acid. After 6 and 21 months of diet, the fatty acid composition and the amounts of endogenous dopaminergic neurotransmitters was assessed in the striatum, the frontal cortex and the hippocampus. The isomerization of a part of dietary alpha-linolenic acid induced some modifications of the levels of endogenous dopaminergic neurotransmitters in all brain areas but was related to a very low incorporation of trans polyunsaturated fatty acids. Increasing the dietary levels of cis alpha-linolenic acid succeeded in correcting the endogenous neurotransmitter concentrations only in the frontal cortex but not in the striatum and the hippocampus. Thus, the levels of dopamine were lowered by 95% in the hippocampus. These results suggest that in addition to the imbalance generated by their presence, trans fatty acids may directly act on the concentration of dopaminergic neurotransmitters.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Release of neurotransmitters in the locus coeruleus.

In the past 15 years the release of neurotransmitters and their metabolites in the locus coeruleus (LC) has been studied by using three approaches: microdialysis; push-pull superfusion; and voltammetry. These sophisticated techniques, which render it possible to follow the time course and magnitude of neurochemical changes in anaesthetized and conscious animals, have permitted great strides towards understanding neurotransmission in the LC. It appears that noradrenaline, known to be released in distant terminal fields, is also released in the somatodendritic area of LC neurons in response to drugs and physiological stimuli. Furthermore, determination of in vivo release enables the identification of functionally important neurotransmitter systems involved in relaying and integrating information reaching the LC via afferent neurons. As outlined in this review, the release rates of glutamate, aspartate, gamma-aminobutyric acid, glycine, 5-hydroxytryptamine and catecholamines, are modified in particular by arousing and stressful stimuli, pain, changes in cardiovascular homeostasis, as well as during opioid withdrawal or the sleep-wake-cycle. Profound interactions also occur between some of the neurotransmitters released during these situations. It appears that individual stimuli produce distinct neurochemical changes which contribute to the regulation of neuronal LC activity. Stimuli that activate LC neurons, such as pain, fall of blood pressure, noise, opiate withdrawal, do not produce a uniform response but modality-specific release patterns of excitatory and inhibitory neurotransmitters within the LC. From these studies and from existing neuroanatomical and electrophysiological data our knowledge of how neurotransmitters work in concert to regulate the functional state of LC noradrenergic perikarya in physiological and pathophysiological conditions is just emerging.

Animals↗
PubMed2003

Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons.

Recent evidence shows that secretory phospholipase A2 (sPLA2) may play a role in membrane fusion and fission, and may thus affect neurotransmission. The present study therefore aimed to elucidate the effects of sPLA2 on vesicle exocytosis. External application of group IIA sPLA2 (purified crotoxin subunit B or purified human synovial sPLA2) caused an immediate increase in exocytosis and neurotransmitter release in pheochromocytoma-12 (PC12) cells, detected by carbon fiber electrodes placed near the cells, or by changes in membrane capacitance of the cells. EGTA and a specific inhibitor of sPLA2 activity, 12-epi-scalaradial, abolished the increase in neurotransmitter release, indicating that the effect of sPLA2 was dependent on calcium and sPLA2 enzymatic activity. A similar increase in neurotransmitter release was also observed in hippocampal neurons after external application of sPLA2, as detected by changes in membrane capacitance of the neurons. In contrast to external application, internal application of sPLA2 to PC12 cells and neurons produced blockade of neurotransmitter release. Our recent studies showed high levels of sPLA2 activity in the normal rat hippocampus, medulla oblongata and cerebral neocortex. The sPLA2 activity in the hippocampus was significantly increased, after kainate-induced neuronal injury. The observed effects of sPLA2 on neurotransmitter release in this study may therefore have a physiological, as well as a pathological role.

Animals↗
PubMed1999

Distribution of neurotransmitter secretion in growing axons.

Neurotransmitter secretion from the nerve terminal is mediated by the fusion of synaptic vesicles with the plasma membrane. It is generally believed that neurotransmitter release in mature synapses is localized to the presynaptic nerve terminals. To probe the topology of neurotransmitter secretion along developing axons in culture, we recorded membrane currents from myocytes manipulated into contact with axons. At the early stages of growth, exocytotic events were detected along the axon as well as at the growth cone. At the later stages of growth, neurotransmitter secretion adopted the form of a smooth proximodistal gradient, with the highest level of activity at the growth cone region. Our results reveal the existence of a previously undetected early stage of axonal growth and suggest developmental regulation in the pattern of neurotransmitter secretion along the growing nerve processes.

Acetylcholine↗