Pituitary Adenylate Cyclase Activating Polypeptide

Abstract

Pituitary adenylate cyclase-activating peptide (PACAP)is an important neuropeptide and immunomodulator in various tissues. Although this peptide and its receptors (ie , VPAC1R , VPAC2R , and PAC1R) are expressed in human skin, their biological roles are unknown. Therefore, we tested whether PACAP regulates vascular responses in human skin in vivo.

Endocannabinoids limit excessive mast cell maturation and activation in human skin

“…M), a key mediator of stress-induced, neurogenic skin inflammation 30 ( Figure 335 6A), and the standard secretagogue, compound 48/80 31 (10 g/ml) ( Figure 6B). Figure 2B-E and Figure S1A Figure 7C) and protein level ( Figures 7A and B).…”

Immunoregulatory Effects of Neuropeptides on Endothelial Cells: Relevance to Dermatological Disorders

“…These receptors have varying levels of expression throughout the skin. Endothelial cells were found to express both VPAC1R and VPAC2R [89] and PACAP-immunoreactive nerve fibers are found in close proximity to dermal blood vessels [90] and mast cells [91]. Of particular interest, VPAC1R expression was not seen in the dermal microvascular endothelial cells of healthy skin but was significant in dermal microvascular endothelial cells of atopic dermatitis and urticaria patients [91].…”

“…Specifically, it appears that PACAP and VIP contribute to the vasodilation and edema seen in the early phase of inflammation in an effort to recruit leukocytes to the site of inflammation [91]. When PACAP was administered intradermally into normal human skin, a dose-dependent and significant wheal and flare reaction developed within minutes [91].…”

“…Endothelial cells were found to express both VPAC1R and VPAC2R [89] and PACAP-immunoreactive nerve fibers are found in close proximity to dermal blood vessels [90] and mast cells [91]. Of particular interest, VPAC1R expression was not seen in the dermal microvascular endothelial cells of healthy skin but was significant in dermal microvascular endothelial cells of atopic dermatitis and urticaria patients [91]. Additionally, PACAP concentration was increased in the skin of psoriasis and urticaria patients [90], and serum VIP levels are increased in patients with atopic dermatitis [92] and psoriasis [57].…”

“…Specifically, it appears that PACAP and VIP contribute to the vasodilation and edema seen in the early phase of inflammation in an effort to recruit leukocytes to the site of inflammation [91]. When PACAP was administered intradermally into normal human skin, a dose-dependent and significant wheal and flare reaction developed within minutes [91]. This finding is consistent with previous studies that showed PACAP-mediated vasodilation and plasma extravasation in rodents after injection into the skin resulting in edema and erythema [95].…”