title: Human β-defensin 2 is a novel opener of Ca2+-activated potassium channels and induces vasodilation and hypotension in monkeys.
abstract: Human β-defensin 2 (HBD2) is a cysteine-rich cationic antimicrobial peptide known for its important role in innate immune system. Intensive studies have demonstrated its antimicrobial and chemotactic activities in vitro. In this study, ELISA analysis showed that HBD2 was significantly downregulated in sera of patients with hypertension. It relaxed vessel smooth muscle by acting on the major regulatory pathways, contributing to vessel smooth muscle contraction. Electrophysiology analysis indicated that HBD2 acted as an opener of large-conductance Ca(2+)-activated potassium (BKCa)-mSlo+hβ1 channels and increased BKCa currents. Mutation analysis revealed that HBD2 activated BKCa-mSlo+hβ1 channels via interacting with Leu41 and Gln43 of β1-loop. In vivo experiments suggested that HBD2 at 4 × to 6 × of physiological concentration exerted hypotensive effect in monkeys significantly, whereas the selective blocker of BKCa channels, Paxilline, inhibited the effect. HBD2 is the first peptide opener of BKCa-mSlo+hβ1 channels. It may be a novel regulator of blood pressure and provides a new therapeutic target for the treatment of hypertension. The HBD2 blockade of the BKCa channels may represent a new type of cross-talk between immune and cardiovascular systems.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Panpan
authors.initials: P
authors.lastname: Hou
authors.forename: Jun
authors.initials: J
authors.lastname: Lang
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Hongli
authors.initials: H
authors.lastname: Yan
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Li
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Huang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wu
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Rong
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Longbao
authors.initials: L
authors.lastname: Lv
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Qiu
authors.forename: Jiuping
authors.initials: J
authors.lastname: Ding
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D007022:Hypotension / Q000097:blood / Q000209:etiology*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010766:Phosphorylation; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014664:Vasodilation; D023083:beta-Defensins / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C106641:DEFB4A protein, human; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D018994:Myosin Light Chains; D024681:Potassium Channels, Calcium-Activated; D011994:Recombinant Proteins; D023083:beta-Defensins; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human; D020742:rhoA GTP-Binding Protein
keywords: Ca2+-activated K+ channels; antimicrobial peptides; hypertension; regional blood flow; β-defensin 2, human