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KMID : 0578320060210030337
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Molecules and Cells
2006 Volume.21 No. 3 p.337 ~ p.342
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Vasoactive Intestinal Polypeptide Inhibits Pacemaker Activity via the Nitric Oxide-cGMP-Protein Kinase G Pathway in the Interstitial Cells of Cajal of the Murine Small Intestine
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Kim Byung-Joo
Lee Jae-Hwan
Jun Jae-Yeoul
Chang In-Youb
So In-Suk
Kim Ki-Whan
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Abstract
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Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous depolarization (pacemaker potentials) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of vasoactive intestinal polypeptide (VIP) on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by whole-cell patch-clamp techniques. Addition of VIP (50 nM-1 mM) decreased the amplitude of pacemaker potentials and depolarized resting membrane potentials. To examine the type of receptors involved in ICC, we examined the effects of the VIP1 agonist and found that it had no effect on pacemaker potentials. Pretreatment with VIP1 antagonist (1 mM) for 10 min also did not block the VIP (50 nM)-induced effects. On the other hand exposure to 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin- 1-one (ODQ, 100 mM), an inhibitor of guanylate cyclase, prevented VIP inhibition of pacemaker potentials. Similarly KT-5823 (1 mM) or RP-8-CPT-cGMPS (10 mM), inhibitors of protein kinase G (PKG) blocked the effect of VIP (50 nM) on pacemaker potentials as did N-nitro-L-arginine (L-NA, 100 mM), a non-selective nitric oxide synthase (NOS) inhibitor. These results imply that the inhibition of pacemaker activity by VIP depends on the NO-cGMP-PKG pathway.
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KEYWORD
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cGMP, Interstitial Cells of Cajal, Nitric Oxide, Protein Kinase G, Vasoactive Intestinal Polypeptide
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