Clofibrate Relaxes the Longitudinal Smooth Muscle of the Mouse Distal Colon through Calcium-Mediated Desensitisation of Contractile Machinery
| Autor: | Kazuhiro Nishiyama, Hidemitsu Nakajima, Yasu-Taka Azuma, Ai Morioka, Tadayoshi Takeuchi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Agonist medicine.medical_specialty Charybdotoxin Colon Pyridines medicine.drug_class Muscle Relaxation Drug Evaluation Preclinical Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor Biology Apamin Mice Myosin-Light-Chain Phosphatase chemistry.chemical_compound Soluble Guanylyl Cyclase Internal medicine Myosin Potassium Channel Blockers medicine Animals Anilides PPAR alpha Channel blocker Clofibrate Receptor Oxazoles Pharmacology chemistry.chemical_classification Anticholesteremic Agents Muscle Smooth General Medicine Cyclic AMP-Dependent Protein Kinases Mice Inbred C57BL Disease Models Animal Pyrimidines Endocrinology chemistry Guanylate Cyclase Benzamides Calcium Marine Toxins Nitric Oxide Synthase Muscle Contraction Sodium Channel Blockers medicine.drug |
| Zdroj: | Pharmacology. 88:65-71 |
| ISSN: | 1423-0313 0031-7012 |
| DOI: | 10.1159/000329418 |
| Popis: | Peroxisome proliferator-activated receptor α (PPAR-α) is a ligand-activated transcription factor that exerts strong effects on metabolic pathways. Our aim was to elucidate the effect of clofibrate, a PPAR-α agonist, on the longitudinal muscle of the mouse distal colon. We initially found that clofibrate induced a relaxation response in this muscle. Notably, the PPAR-α antagonists GW9662 and T0070907 did not attenuate this clofibrate-induced relaxation. The structurally related PPAR-α agonists fenofibrate and bezafibrate induced relaxation in the distal colon as effectively as clofibrate. In contrast, wy-14643, which activates PPAR-α more selectively than clofibrate, had no effect. Furthermore, clofibrate-induced relaxation was not affected by N-nitro-L-arginine, an NO synthase inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3- a]quinoxaline-1-one, a soluble guanylate cyclase inhibitor, or H89, a protein kinase A inhibitor. Tetrodotoxin, an Na+ channel blocker, and glibenclamide, apamin, charybdotoxin and XE991, various K+ channel blockers, had no effect on clofibrate-induced relaxation. Importantly, clofibrate induced a relaxation response that was not accompanied by any alteration in the cytoplasmic Ca2+ concentration in the longitudinal muscle of the mouse distal colon. Moreover, calyculin A, a myosin light-chain phosphatase (MLCP) inhibitor, attenuated clofibrate-induced relaxation. Our findings indicate that clofibrate relaxes the longitudinal smooth muscle of the mouse distal colon by regulating MLCP activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|