Capsaicin-induced, capsazepine-insensitive relaxation of the guinea-pig ileum.
The mechanisms underlying transient receptor potential vanilloid receptor type 1 (TRPV1)-independent relaxation elicited by capsaicin were studied by measuring isometric force and phosphorylation of 20-kDa regulatory light chain subunit of myosin (MLC(20)) in ileum longitudinal smooth muscles of guinea-pigs. In acetylcholine-stimulated tissues, capsaicin (1-100 microM) and resiniferatoxin (10 nM-1 microM) produced a concentration-dependent relaxation. The relaxant response was attenuated by 4-aminopyridine and high-KCl solution, but not by capsazepine, tetraethylammonium, Ba(2+), glibenclamide, charybdotoxin plus apamin nor antagonists of cannabinoid receptor type 1 and calcitonin-gene related peptide. A RhoA kinase inhibitor reduced the relaxant effect of capsaicin at 30 microM. Capsaicin and resiniferatoxin reduced acetylcholine- and caffeine-induced transient contractions in a Ca(2+)-free, EGTA solution. Capsaicin at 30 microM for 20 min did not alter basal levels of MLC(20) phosphorylation, but abolished an increase by acetylcholine in MLC(20) phosphorylation. It is suggested that the relaxant effect of capsaicin at concentrations used is not mediated by TRPV1, but by 4-aminopyridine-sensitive K(+) channels, and that capsaicin inhibits contractile mechanisms involving Ca(2+) release from intracellular storage sites. The relaxation could be explained by a decrease in phosphorylation of MLC(20).
Fujimoto
Seigo
S
Department of Cellular and Molecular Pharmacology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-cho, Mizuho-ku, Japan. fujimoto@med.nagoya-cu.ac.jp
Mori
Mayumi
M
Tsushima
Hiromi
H
Kunimatsu
Mitoshi
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D019789:Tetraethylammonium / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D054460:rho-Associated Kinases
D001578:Benzopyrans; D004224:Diterpenes; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014665:Vasodilator Agents; D018999:Charybdotoxin; C058636:calcitonin gene-related peptide (8-37); D004008:Diclofenac; D019335:Nitroarginine; D001030:Apamin; D001464:Barium; D002110:Caffeine; C103505:AM 251; D019789:Tetraethylammonium; D011189:Potassium Chloride; C024353:resiniferatoxin; D015761:4-Aminopyridine; D010208:Papaverine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D000109:Acetylcholine; C074338:Y 26763; D002211:Capsaicin; D005905:Glyburide; D002118:Calcium; D004121:Dimethyl Sulfoxide; D006145:Guanethidine