Therefore, it is possible that the two populations of amperometric spikes correspond to two modes of vesicle fusion with different rates of fusion pore dilation rather than two groups of vesicles. Our data demonstrate that the distribution of decay time of both fast and slow spikes is shifted to longer times by the treatment of L-DOPA owing to increased vesicular volume. Considering only the effect of vesicular size, one would expect the distribution of decay time in PACAP-treated cells to be similar to the trend observed in L-DOPA-treated cells. In contrast, a significant fraction of the fast spikes have been transformed into slow spikes by treatment with PACAP. Data from Darchen’s group indicate that fast and slow fusion events employ different machineries, in which SNARE proteins have a key role in membrane fusion. To date, little work has been done to illustrate whether PACAP regulates SNARE complex assembling and structural transition, more experiments are necessary to explain the machinery BAY-60-7550 cost involved in the effect of PACAP on the rate of exocytosis. In this study, we demonstrate that PACAP increases quantal release induced by high K+ and vesicular volume, without significantly regulating the frequency of vesicle fusion events.

Also, we examine the effects of PACAP and L-DOPA on exocytosis in PC12 cells. Despite both PACAP and L-DOPA appear to stabilize fusion pore formation, different dynamics of fusion pores in PACAP- and L-DOPA-treated cells are observed. Furthermore, PACAP might regulate the transformation of fast fusion events into slow fusion events, without similar transformation seen in L-DOPA-treated PC12 cells. PACAP might affect the structures associated with exocytosis as well as vesicle size, while the effect of L-DOPA on exocytosis is likely attributed to increased vesicle volume. Due to its multiple putative influences on dopaminergic neurons, PACAP might not only provide dopamine modulation, but also render potential neuroprotective and restorative therapy for PD patients. Ischemic stroke is the second most common cause of death and the major cause of disability worldwide. According to the American Heart Association, someone has a stroke every 40 seconds, and stroke accounts for one of every 18 deaths in the United States. The sudden reduction in blood flow leads to decreased oxygen and glucose supplies to the ischemic brain area, resulting in a failure of cellular bioenergetics.

This condition triggers a series of events known as the ischemic cascade, during which the degree of damage is dependent on the affected area and length of blood flow blockage. Disruption of brain metabolism is clearly a key element in stroke, resulting in cellular damage and impairment of neurological functions. Both excitotoxicity and oxidative damage are ischemic events related to cerebral energy failure. Due to energy depletion, excitatory amino acid transporters, EAAT1/glutamateaspartate transporter and EAAT2/glutamate transporter-1 in astrocytes and EAAT3/excitatory amino acid carrier 1 in neurons, responsible for glutamate uptake.