Differences between

axon terminals and cell bodies may also be found in systems that reduce calcium, including mitochondria, plasma membrane calcium pumps, and sodium/calcium exchangers ( Dayanithi et al., 2012). Finally, ATP coreleased from magnocellular neurons exerts different feedback effects on axon terminals and cell bodies, potentially differentially regulating peptide release, in part due to different sets of ATP receptors on axons and cell bodies ( Lemos et al., 2012). Calcium can also be released into the cytoplasm from intracellular stores, particularly the endoplasmic reticulum. Oxytocin, or agents AZD6738 concentration such as thapsigargin that induce calcium release from intracellular stores into the cytoplasm, can directly evoke dendritic release of oxytocin or vasopressin independent selleck screening library of action potentials (Lambert et al., 1994; Ludwig et al., 2002). Release of intracellular calcium can also prime the system for enhanced release upon subsequent increases in electrical activity ( Ludwig et al., 2002; Ludwig and Leng, 2006). Oxytocin receptor activation induces phospholipase C resulting in production of IP3 and subsequent release of calcium from the endoplasmic reticulum. This priming enhances the subsequent release of oxytocin,

potentially related to actin-dependent movement of peptide-containing granules toward the plasma membrane ( Tobin and Ludwig, 2007; Leng et al., 2008). Priming of oxytocin-laden DCVs, in part by movement of the DCVs to a position closer to the plasma membrane, allows a substantial amplification Calpain of oxytocin release with subsequent electrical activity. Interestingly, priming with thapsigargin can increase the K+-mediated depolarization-induced oxytocin release for an extended period of 90 min ( Ludwig et al., 2002). Priming of DCV release has been studied outside

the brain, particularly in pituitary cells that synthesize luteinizing hormone; axonal release of GnRH from preoptic neurons into the portal blood supply of the median eminence primes the luteinizing hormone cells by multiple mechanisms to show an enhanced release in response to subsequent GnRH stimulation ( Leng et al., 2008; Fink, 1995). Differential expression of proteins involved in exocytosis in dendrites and axon terminals may also account for differences in release. In magnocellular axon terminals in the neurohypophysis, VAMP-2, SNAP-25, and syntaxin-1 are found near oxytocin and vasopressin-containing dense core vesicles; in contrast, the dendrites of the same cell type contain syntaxin-1, but SNAP-25, VAMP-2 and synaptotagmin-1 show no colocalization with oxytocin or vasopressin (Tobin et al., 2012). Synthesis of neuropeptides generally occurs in the cell body, but has also been reported in dendrites.