However, in the present investigation, we directly demonstrated that PAR2 activation with a synthetic activating peptide, as well as physiological stimulator such as trypsin, significantly induced airway gland mucus secretion. Comparing secretion rates with previous studies in which we used the same methods, the secretion rate induced by PAR2-AP in the human gland was approximately 30% of that induced by carbachol treatment but higher than the responses induced by VIP or substance P. In addition, tiny bubbles were observed on the airway surface after treatment with PAR2, but the bubbles did not become bigger despite continuous stimulation. This Niltubacin suggests that the main target of PAR2 is the submucosal gland and not the airway surface epithelium. Although PAR2 is mainly expressed in serous cells of the airway gland, the protein content and lysozyme concentration of PAR-2 induced mucus does not differ from that of carbacholinduced mucus. Therefore it remains necessary to elucidate whether PAR2-AP stimulated mucus secretion only from serous cells or from other cells as well. Although the parasympathetic pathway primarily controls airway gland secretion, evidence increasingly supports a role for intrinsic control systems for airway gland secretion, such as the capsaicin-sensitive C-fiber system. In our experiments, endogenous PAR2 agonists, such as airway trypsin and neutrophil elastase, also stimulated airway mucus secretion from the submucosal gland. This local receptor-mediated mucus secretion may be involved in host defense against pathogens in airway mucosa, which is independent of parasympathetic control. Furthermore, because the PAR2-AP-induced mucus system is independent of the CFTR, this mechanism would be preserved in the airways of patients with CF and could act as a salvaged route for fluid secretion and innate immune responses. We plan to investigate this system in CF patients. Interestingly, PAR2 expression is increased in airway epithelial cells in allergic airway disease and in bronchial vessels of patients with bronchitis. Furthermore, human airway tryptase is detected in high levels in BAL fluid from patients with chronic airway inflammatory disease. Although not shown, our recent data also revealed that PAR2 expression in the airway glands is increased in patients with allergic rhinitis. Thus, PAR2 upregulation may represent an underlying mechanism of mucus hypersecretion in allergic or inflammatory airway disease. In summary, we demonstrated that PAR2-AP increases mucus secretion from the airway glands of three different species and that this effect is Ca2+ dependent and at least partially CFTR-independent. Interestingly, although we observed an increase in the number of immature neurons in the striatum, LV-Wnt3a-HA injection into the SVZ was not associated with an increase in the number of mature neurons. This suggests that the local effect on proliferation in the SVZ is insufficient for neuronal regeneration. Thus, if the environment in the ischemic striatum does not change, the new neurons cannot survive. Wnt family gene mRNA is detected in the SVZ, but there is no upregulation of these genes after stroke.