Pituitary adenylate cyclase activating polypeptide: An important vascular regulator in human skin in vivo

Stephan Seeliger, Jörg Buddenkotte, Anjona Schmidt-Choudhury, Carine Rosignoli, Victoria Shpacovitch, Ulrike Von Arnim, Dieter Metze, Roman Rukwied, Martin Schmelz, Ralf Paus, Johannes J. Voegel, Wolfgang E. Schmidt, Martin Steinhoff

Research output: Contribution to journalArticle

36 Citations (Scopus)

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. When injected intravenously, PACAP induced a significant, concentration-dependent vascular response (ie, flush, erythema, edema) and mediated a significant and concentration-dependent increase in intrarectal body temperature that peaked at 2.7°C. Topical application of PACAP induced marked concentration-dependent edema. Immunohistochemistry revealed a close association of PACAP-immunoreactive nerve fibers with mast cells and dermal blood vessels. VPAC1R was expressed by dermal endothelial cells, CD4+ and CD8+ T cells, mast cells, and keratinocytes, whereas VPAC2R was expressed only in keratinocytes. VPAC1R protein and mRNA were also detected in human dermal microvascular endothelial cells. The PACAP-induced change in cAMP production in these cells demonstrated VPAC1R to be functional. PACAP treatment of organ-cultured human skin strongly increased the number of CD31+ vessel cross-sections. Taken together, these results suggest that PACAP directly induces vascular responses that may be associated with neurogenic inflammation, indicating for the first time that PACAP may be a crucial vascular regulator in human skin in vivo. Antagonists to PACAP function may be beneficial for the treatment of inflammatory skin diseases with a neurogenic component.

Original languageEnglish (US)
Pages (from-to)2563-2575
Number of pages13
JournalAmerican Journal of Pathology
Volume177
Issue number5
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Pituitary Adenylate Cyclase-Activating Polypeptide
Adenylyl Cyclases
Blood Vessels
Skin
Peptides
Keratinocytes
Mast Cells
Edema
Endothelial Cells
Neurogenic Inflammation
Peptide Receptors
Immunologic Factors
Erythema
Neuropeptides
Body Temperature
Nerve Fibers
Skin Diseases
Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Seeliger, S., Buddenkotte, J., Schmidt-Choudhury, A., Rosignoli, C., Shpacovitch, V., Von Arnim, U., ... Steinhoff, M. (2010). Pituitary adenylate cyclase activating polypeptide: An important vascular regulator in human skin in vivo. American Journal of Pathology, 177(5), 2563-2575. https://doi.org/10.2353/ajpath.2010.090941

Pituitary adenylate cyclase activating polypeptide : An important vascular regulator in human skin in vivo. / Seeliger, Stephan; Buddenkotte, Jörg; Schmidt-Choudhury, Anjona; Rosignoli, Carine; Shpacovitch, Victoria; Von Arnim, Ulrike; Metze, Dieter; Rukwied, Roman; Schmelz, Martin; Paus, Ralf; Voegel, Johannes J.; Schmidt, Wolfgang E.; Steinhoff, Martin.

In: American Journal of Pathology, Vol. 177, No. 5, 01.01.2010, p. 2563-2575.

Research output: Contribution to journalArticle

Seeliger, S, Buddenkotte, J, Schmidt-Choudhury, A, Rosignoli, C, Shpacovitch, V, Von Arnim, U, Metze, D, Rukwied, R, Schmelz, M, Paus, R, Voegel, JJ, Schmidt, WE & Steinhoff, M 2010, 'Pituitary adenylate cyclase activating polypeptide: An important vascular regulator in human skin in vivo', American Journal of Pathology, vol. 177, no. 5, pp. 2563-2575. https://doi.org/10.2353/ajpath.2010.090941
Seeliger S, Buddenkotte J, Schmidt-Choudhury A, Rosignoli C, Shpacovitch V, Von Arnim U et al. Pituitary adenylate cyclase activating polypeptide: An important vascular regulator in human skin in vivo. American Journal of Pathology. 2010 Jan 1;177(5):2563-2575. https://doi.org/10.2353/ajpath.2010.090941
Seeliger, Stephan ; Buddenkotte, Jörg ; Schmidt-Choudhury, Anjona ; Rosignoli, Carine ; Shpacovitch, Victoria ; Von Arnim, Ulrike ; Metze, Dieter ; Rukwied, Roman ; Schmelz, Martin ; Paus, Ralf ; Voegel, Johannes J. ; Schmidt, Wolfgang E. ; Steinhoff, Martin. / Pituitary adenylate cyclase activating polypeptide : An important vascular regulator in human skin in vivo. In: American Journal of Pathology. 2010 ; Vol. 177, No. 5. pp. 2563-2575.
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