Vesicular hypothesis

ACh release. According to the classical, vesicular hypothesis (Del Castillo Katz, 1954) packets of transmitter molecules ( quantums ) contained in synaptic vesicles are released by exocytosis. The vesicular hypothesis was in accordance with morphological studies demonstrating the existence of synaptic vesicles (De Roberties Bennett, 1954) and explained the discrete nature of the postsynaptic response, namely the occurrence of miniature-endplate potentials (Fatt Katz 1952). Alternative hypotheses (e.g. Israel Dunant, 1979 Tauc, 1979) are based on experimental observations of the release of cytoplasmic ACh. 

Approximately 30 years ago, Schildkraut postulated that noradrenaline may play a pivotal role in the aetiology of depression. Evidence in favour of this hypothesis was provided by the observation that the antihypertensive drug reserpine, which depletes both the central and peripheral vesicular stores of catecholamines such as noradrenaline, is likely to precipitate depression in patients in remission. The experimental drug alpha-methyl-paratyrosine that blocks the synthesis of noradrenaline by inhibiting the rate-limiting enzyme tyrosine hydroxylase was also shown to precipitate depression in patients during remission. While such findings are only indirect indicators that noradrenaline plays an important role in human behaviour, and may be defective in depression, more direct evidence is needed to substantiate the hypothesis. The most obvious approach would be to determine the concentration of noradrenaline and/or its major central... 

Available evidence indicates that CNTs do not enter the cell directly from the plasma membrane, but are endocytosed inside the lumen of vesicular structures in a temperature- and energy-dependent process (Black and Dolly 1986 Critchley et al. 1985 Dolly et al. 1984 reviewed in Schiavo et al. 2000). The finding of SV proteins as receptors of BoNTs support the proposal (Montecucco and Schiavo 1995) that, after binding, BoNTs are endocytosed within synaptic vesicles (SV) via their retrieval to be refilled with neurotransmitter, an hypothesis originally advanced to account for the increased rate of poisoning with NMJ activity (Figure 4) (Hughes and Whaler 1962). 

The mechanism by w hich immunoUposomes penetrate across the BBB is not fully understood. It w as hypothesized that the process involves the binding of immunoliposomes to multiple capillary luminal membrane receptors, fusion of the liposomes with several vesicular pits into a large vesicle and transcytosis of this vesicle to the abluminal membrane border (Comford and Comford, 2002). Studies by electron microscopy support this hypothesis (Faustmann andDermietzel, 1985). 

Truant, R., R. Atwal, and A. Burtnik. Hypothesis Huntingtin may function in membrane association and vesicular trafficking. 84(6), 2006 912—7. 

When vesicles are polymerised, the interaction between substrate and vesicle is modified. We therefore expect different reactivities for monomer vesicles and their polymerised counterparts. This hypothesis has been borne out experimentally with regard to hydrolysis and aminolysis of nitrophenylesters. Polymerisation allows better control of reactivity by localising the substrate at different vesicular sites. 

Two separate sets of experiments appear to refute the hypothesis of simultaneous internal initiation of VSV transcripts. By studying kinetics of mRNA synthesis analyzed by specific RNase Ti oligonucleotides complementary to the N, NS, and M genes, Iverson and Rose (1982) obtained results inconsistent with a model of Vesicular stomatitis virus transcription involving simultaneous initiation and presynthesis of leader RNAs 30-70 nucleotides long for each mRNA. Emerson (1982), in very different experiments, found by... 

High retention of the drug in these compartments can be explained by protonation of the drug molecules in the acidic compartments, which reduces their ability to diffuse across vesicular membranes. The fact that ionophoric compounds, such as nigoricin and monensin, reverse multidrug resistance by redueing pH gradients in the cytoplasm supports this hypothesis. 

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