Bioenergetics of secretory vesicles

Njus, David; Kelley, Patrick M.; Harnadek, Gordon J.

doi:10.1016/0304-4173(87)90003-6

Cited by 206 publications

(139 citation statements)

References 221 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…It is known that 5-HT can passively cross the membrane of intracellular acidic organelles where it is protonated and remains trapped because charged monoamines cannot cross back membranes. In view of pH differences between vesicles and axoplasm, there could be at least a 100-fold increase in [ 3 H]5-HT vesicular concentration compared with the axoplasm (Njus et al, 1986), although this passively generated gradient remains very small compared with that generated by VMAT2, it may nevertheless be a way to compensate for VMAT2 loss. (3) Finally, there is evidence for uptake of 5-HT in catecholaminergic neurons (Cases et al, 1998;Zhou et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Narboux-Nême

Sagné

Doly

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

The vesicular monoamine transporter type 2 gene (VMAT2) has a crucial role in the storage and synaptic release of all monoamines, including serotonin (5-HT). To evaluate the specific role of VMAT2 in 5-HT neurons, we produced a conditional ablation of VMAT2 under control of the serotonin transporter (slc6a4) promoter. VMAT2 sertÀcre mice showed a major (À95%) depletion of 5-HT levels in the brain with no major alterations in other monoamines. Raphe neurons contained no 5-HT immunoreactivity in VMAT2 sertÀcre mice but developed normal innervations, as assessed by both tryptophan hydroxylase 2 and 5-HT transporter labeling. Increased 5-HT 1A autoreceptor coupling to G protein, as assessed with agonist-stimulated [ 35 S]GTP-g-S binding, was observed in the raphe area, indicating an adaptive change to reduced 5-HT transmission. Behavioral evaluation in adult VMAT2 sertÀcre mice showed an increase in escape-like reactions in response to tail suspension and anxiolytic-like response in the novelty-suppressed feeding test. In an aversive ultrasoundinduced defense paradigm, VMAT2 sertÀcre mice displayed a major increase in escape-like behaviors. Wild-type-like defense phenotype could be rescued by replenishing intracellular 5-HT stores with chronic pargyline (a monoamine oxidase inhibitor) treatment. Pargyline also allowed some form of 5-HT release, although in reduced amounts, in synaptosomes from VMAT2 sertÀcre mouse brain. These findings are coherent with the notion that 5-HT has an important role in anxiety, and provide new insights into the role of endogenous 5-HT in defense behaviors.

show abstract

Section: Discussionmentioning

confidence: 99%

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Narboux-Nême

Sagné

Doly

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…It is thus established that, e.g. chromaffin cells and the closely related PC12 cells store large amounts of ATP (>100 mM) together with catecholamines [2,102], that insulin secretion from B cells occurs together with ATP [17] and that α-dense granules in thrombocytes contain very high concentrations of ADP, a known key factor in thrombus formation [14]. There is strong evidence that astrocytic release of nucleotides under physiological conditions involves an exocytotic mechanism [45,103,104], in contrast to the above-mentioned controversial issue of connexon hemichannel-mediated ATP release from astrocytes under non-physiological situations [36].…”

Section: Vesicular Release Of Nucleotidesmentioning

confidence: 99%

ATP release from non-excitable cells

Praetorius

Leipziger

2009

Purinergic Signalling

205

229

View full text Add to dashboard Cite

All cells release nucleotides and are in one way or another involved in local autocrine and paracrine regulation of organ function via stimulation of purinergic receptors. Significant technical advances have been made in recent years to quantify more precisely resting and stimulated adenosine triphosphate (ATP) concentrations in close proximity to the plasma membrane. These technical advances are reviewed here. However, the mechanisms by which cells release ATP continue to be enigmatic. The current state of knowledge on different suggested mechanisms is also reviewed. Current evidence suggests that two separate regulated modes of ATP release co-exist in nonexcitable cells: (1) a conductive pore which in several systems has been found to be the channel pannexin 1 and (2) vesicular release. Modes of stimulation of ATP release are reviewed and indicate that both subtle mechanical stimulation and agonist-triggered release play pivotal roles. The mechano-sensor for ATP release is not yet defined.

show abstract

“…Probably as little as four transport proteins account for accumulation of transmitter in synaptic vesicles: the acetylcholine transporter (Koeningsberger and Parsons, 1980), a GABA/glycine transporter (Fyske and Fonnum, 1988;Hell et al, 1988;Kish et al, 1989), a glutamate carrier (Disbrow et al, 1982;Naito and Ueda, 1983;Maycox et al, 1988) and a non-specific monoamine carrier (see Njus et al, 1986;Erickson et al, 1992;Liu et al, 1992). Large, dense-cored vesicles may only contain the monoamine carrier and contain peptides that they have received while budding from the Golgi apparatus.…”

Section: The Availability Of Transmitters For Releasementioning

confidence: 99%

“…Constant supply of these proteins is thus necessary, for which the only likely source is the protein synthesis in the cell soma. Furthermore, pharmacological manipulations (summarized in McGeer et al, 1987) suggests that vesicles are packaged with monoamines in the cell soma and thcn migrate to the terminals by axonal transport, although it is clear that small synaptic vesicles can locally synthesize and accumulate monaminc transmitters (Smith, 1972;Njus et al, 1986;Maycox et al, 1990). It has been assumed that the presynaptic neuron may exhibit plastic properties both in targeting of neuropeptide containing vesicles and the intraceltular cleavage of precursor peptides.…”

Section: Differential Transmitter Release: Co-transmission and Changementioning

confidence: 99%