日本語フィールド
著者：*Masaaki Kurahashi, Salah A Baker, Yoshihiko Kito, Allison Bartlett, Masayasu Hara, Hiromitsu Takeyama, Hikaru Hashitani, Kenton M Sanders題名：PDGFRα + Interstitial Cells are Effector Cells of PACAP Signaling in Mouse and Human Colon発表情報：Cell Mol Gastroenterol Hepatol 巻: 14 号: 2 ページ: 357-373キーワード：Colon; Inhibitory Effects; Interstitial Cells; Peptidergic Neurotransduction概要：Background & aims: Platelet-derived growth factor receptor α (PDGFRα)-positive interstitial cells (PICs) are interposed between enteric nerve fibers and smooth muscle cells (SMCs) in the tunica muscularis of the gastrointestinal tract. PICs have robust expression of small conductance Ca2+ activated K+ channels 3 (SK3 channels) and transduce inhibitory inputs from purinergic and sympathetic nerves in mouse and human colon. We investigated whether PICs also express pituitary adenylate cyclase-activating polypeptide (PACAP) receptors, PAC1 (PAC1R), and are involved in mediating inhibitory regulation of colonic contractions by PACAP in mouse and human colons.
Methods: Gene expression analysis, Ca2+ imaging, and contractile experiments were performed on mouse colonic muscles. Ca2+ imaging, intracellular electrical recordings, and contractile experiments were performed on human colonic muscles.
Results: Adcyap1r1 (encoding PAC1R) is highly expressed in mouse PICs. Interstitial cells of Cajal and SMCs expressed far lower levels of Adcyap1r. Vipr1 and Vipr2 were expressed at low levels in PICs, interstitial cells of Cajal, and SMCs. PACAP elicited Ca2+ transients in mouse PICs and inhibited spontaneous phasic contractions via SK channels. In human colonic muscles, PAC1R agonists elicited Ca2+ transients in PIC, hyperpolarized SMCs through SK channels and inhibited spontaneous phasic contractions.
Conclusions: PICs of mouse and human colon utilize PAC1R-SK channel signal pathway to inhibit colonic contractions in response to PACAP. Effects of PACAP are in addition to the previously described purinergic and sympathetic inputs to PICs. Thus, PICs integrate inhibitory inputs from at least 3 neurotransmitters and utilize several types of receptors to activate SK channels and regulate colonic contractile behaviors.抄録：英語フィールド
Author：*Masaaki Kurahashi, Salah A Baker, Yoshihiko Kito, Allison Bartlett, Masayasu Hara, Hiromitsu Takeyama, Hikaru Hashitani, Kenton M SandersTitle：PDGFRα + Interstitial Cells are Effector Cells of PACAP Signaling in Mouse and Human ColonAnnouncement information:Cell Mol Gastroenterol Hepatol Vol: 14 Issue: 2 Page: 357-373Keyword：Colon; Inhibitory Effects; Interstitial Cells; Peptidergic NeurotransductionAn abstract：Background & aims: Platelet-derived growth factor receptor α (PDGFRα)-positive interstitial cells (PICs) are interposed between enteric nerve fibers and smooth muscle cells (SMCs) in the tunica muscularis of the gastrointestinal tract. PICs have robust expression of small conductance Ca2+ activated K+ channels 3 (SK3 channels) and transduce inhibitory inputs from purinergic and sympathetic nerves in mouse and human colon. We investigated whether PICs also express pituitary adenylate cyclase-activating polypeptide (PACAP) receptors, PAC1 (PAC1R), and are involved in mediating inhibitory regulation of colonic contractions by PACAP in mouse and human colons.
Methods: Gene expression analysis, Ca2+ imaging, and contractile experiments were performed on mouse colonic muscles. Ca2+ imaging, intracellular electrical recordings, and contractile experiments were performed on human colonic muscles.
Results: Adcyap1r1 (encoding PAC1R) is highly expressed in mouse PICs. Interstitial cells of Cajal and SMCs expressed far lower levels of Adcyap1r. Vipr1 and Vipr2 were expressed at low levels in PICs, interstitial cells of Cajal, and SMCs. PACAP elicited Ca2+ transients in mouse PICs and inhibited spontaneous phasic contractions via SK channels. In human colonic muscles, PAC1R agonists elicited Ca2+ transients in PIC, hyperpolarized SMCs through SK channels and inhibited spontaneous phasic contractions.
Conclusions: PICs of mouse and human colon utilize PAC1R-SK channel signal pathway to inhibit colonic contractions in response to PACAP. Effects of PACAP are in addition to the previously described purinergic and sympathetic inputs to PICs. Thus, PICs integrate inhibitory inputs from at least 3 neurotransmitters and utilize several types of receptors to activate SK channels and regulate colonic contractile behaviors.