Mechanism of Carbon Monoxide-Induced Relaxation in the Guinea Pig Ileal Smooth Muscle.

Abstract

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.

Carbon monoxide activates human intestinal smooth muscle L-type Ca2+ channels through a nitric oxide-dependent mechanism

“…The present studies suggest that CO can, in fact, activate the nNOS/NO/ cGMP pathway, confirming that at low concentrations, CO is as an agonist of NO production. This is in contrast to a previously reported study in another species that suggested that CO had little effect on peak I Ba in guinea pig ileal muscle (22). However, a much higher concentration of CO was used, which may have inhibited NO production.…”

Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications

“…The effect of CO on voltage-dependent calcium channels in guinea pig ileum smooth muscle cells was directly studied using the whole-cell patch clamp technique. CO (100 M) had little effect on the peak Ba 2ϩ currents (I Ba ) when voltage was stepped from Ϫ60 614 to ϩ50 mV (holding potential, Ϫ60 mV) (Kwon et al, 2001). It was thus concluded that the relaxant effect of CO on this tissue was not due to inhibition of L-type Ca 2ϩ channels.…”