Figure 2.
illustrates the vascular function of three neuropeptides released from capsaicin-sensitive nerves mainly. (1) Inflammatory factors, such as TNFα can active TRPV1 to release pro- and anti-inflammatory neuropeptides after binding to receptors adjoined to TRPV1. (2) combination of CGRP receptors on SMCs can decrease [Ca2+]i to cause vasorelaxation by activating AC/cAMP/PKA pathway, which opens K+ channels and inhibits calcium influx, and can inhibit SMC proliferation by upregulate P53 and P27. And if combined to endothelial cells, it can stimulate NO production, which diffuses into SMC to cause relaxation. Besides, CGRP can produce vasodilation indirectly by inhibiting ET-1 binding to its receptors. (3) SP combined to endothelial cells can dilate vessels via the eNOS/NO way. (4) SST can inhibit CGRP/SP release and TRPV1 activation. (5) TRPV1, CGRP, SP, and SST can mediate activities of inflammatory cells and productions of inflammatory factors by promoting or inhibiting expression of NF-kB. CGRP: calcitonin gene related peptide. SP: substance P. SST: somatostatin. TNFα: tumor necrosis factor α. ET-1 endothelin-1. TRPV1: transient receptor potential vanilloid subfamily member 1. VDC: Voltage-independent calcium channel. AC: adenylate cyclase. cAMP: cyclic adenosine monophosphate. PKA: protein kinase A. NO: nitric oxide. eNOS: endothelial nitric oxide synthase. NF-kB: nuclear factor-kappa B.