G protein-coupled receptors (GPCRs) represent the largest receptor protein family and form part of a complex information processing system used to modulate neurotransmitter release in the nervous system. Aberrant signalling and excess neurotransmission in -for example- the peripheral nervous system is associated with cardiovascular disorders or chronic and inflammatory pain. Understanding the complex interplay between GPCR signalling and the exocytotic machinery in health and disease is therefore pivotal.Previously we showed that activation of Gq protein-coupled H1 histamine receptors potentiates stimulus-coupled exocytosis in bovine neuroendocrine chromaffin cells despite inhibiting Ca2+ influx through voltage-gated calcium channels (VGCCs)[1]. This potentiation is restricted to the immediately releasable pool (IRP) of vesicles tightly coupled to VGCCs and requires the SNARE priming protein Munc13-1. Doc2B is a high affinity calcium-binding protein known to interact with Munc13-1 to promote exocytosis; whether it plays a role in agonist-regulated exocytosis is unknown. To address this question, we isolated chromaffin cells from adult Doc2B (+/+), (+/-) and (-/-) mice and examined the effects of PLC-coupled GqPCR receptor activation on depolarization-evoked exocytosis, measured as changes in membrane capacitance. We found that like in neurons, stimulus-coupled synchronous exocytosis (evoked by a 40 or 200 ms depolarization from -80 to +10 mV) was not significantly different between Doc2B (+/+), (+/-) and (-/-) cells. In contrast, asynchronous release was significantly increased in Doc2B (-/-) cells demonstrating a regulatory role of Doc2B in Ca2+-evoked asynchronous release. Replacing Ca2+ by Ba2+ however showed that Doc2B is not the sensor for Ba2+-mediated asynchronous release.Finally, although more than 80 % of mouse chromaffin cells, independent of their genotype, responded to 100uM histamine with a reduction of Ca2+ influx, potentiation of exocytosis was surprisingly modest (2-fold) and was rarely observed in all three genotypes ((+/+): 5/17 cells, (+/-): 5/24 cells, (-/-): 2/18). This is in stark contrast to bovine cells, where 80 % of the cells show a 5-fold potentiation of exocytosis from the IRP and RRP. Importantly, bypassing GPCRs by using the diacylglycerol analog PMA, mouse chromaffin cells responded with potentiation of exocytosis from the RRP, but not the IRP; another difference to their bovine equivalent. Taken together, the results suggest that there are profound species differences in the organization of the secretory machinery, VGCCs and its regulation by GqPCRs in neuroendocrine cells.