Mechanism of carbon monoxide-induced relaxation in the guinea pig ileal smooth muscle.
The mechanism of carbon monoxide (CO)-induced relaxation were investigated in the guinea-pig ileum. CO (10%) inhibited the 40 mM KCl-induced contraction. This effect was antagonized by ODQ (1 microM), a soluble guanylate cyclase inhibitor. In contrast, CO did not inhibit the 40 mM KCl-induced increase in cytosolic Ca2+ level ([Ca2+]i). Cumulative addition of KCl induced a graded increase in both [Ca2+]i and muscle tension. In the presence of CO, the increase in muscle tension was attenuated whereas the increase in [Ca2+]i was only slightly decreased. Thus, the [Ca2+]i-tension relationship constructed by cumulative addition of KCl shifted downwards in the presence of CO. Using the patch clamp, CO was found to have little effect on the peak Ba currents (I(Ba)) when voltage was stepped from -60 mV to 0 mV. From these results, we conclude that CO inhibits contraction of guinea-pig ileum mainly by the decrease in the sensitivity of contractile elements to Ca2+ via a cyclic GMP-dependent pathway but not by the inhibition of L-type Ca2+ channel.
Kwon
S
S
Department of Physiology, College of Medicine, Yonsei University, Seoul, Korea.
Chung
S
S
Ahn
D
D
Yeon
D
D
Nam
T
T
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000097:blood / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002248:Carbon Monoxide / Q000494:pharmacology*; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D016257:Fura-2 / Q000031:analogs & derivatives / Q000737:chemistry; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010069:Oxadiazoles; D011810:Quinoxalines; C049925:fura-2-am; D011189:Potassium Chloride; D002248:Carbon Monoxide; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2