Carbon monoxide inhibits depolarization-induced Ca rise and increases cyclic GMP in visceral smooth muscle cells.
Monocytes were isolated from the urinary bladder of the guinea-pig. By means of the voltage clamp technique, whole cells were depolarized from -65 to +10 mV in order to increase the intracellular calcium concentration [Ca2+]i and to monitor this increase by means of the calcium activated potassium current IK.Ca. Superfusion of the cells with carbon monoxide-containing solutions for 2 min inhibited the signal to about 50% of the control suggesting depression of the depolarization-induced increase in [Ca2+]i. The CO-mediated inhibition of IK.Ca was partially reversed by wash-off of CO; flashes of high light intensity accelerated the rate of recovery. Sodium nitroprusside (0.01-1 mM) depressed the depolarization-induced increase in [Ca2+]i similar to CO. In multicellular preparations of the urinary bladder, CO-containing media were shown to increase the cGMP concentration by a factor of 2 in the absence and by a factor of 3 in the presence of 1 mM of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX). According to our previous work, CO binds to and activates soluble guanylate cyclase [Brüne B and Ullrich V, Mol Pharmacol 32: 497-504, 1987; Utz J and Ullrich V, Naunyn Schmiedebergs Arch Pharmacol 337 (Suppl): 299, 1988] and the rise in cGMP could thus effect [Ca2+]i by still unknown mechanisms.
Trischmann
U
U
Institute of Physiology, University of Köln, Federal Republic of Germany.
Klöckner
U
U
Isenberg
G
G
Utz
J
J
Ullrich
V
V
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002248:Carbon Monoxide / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D004553:Electric Conductivity; D006168:Guinea Pigs; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside; D001743:Urinary Bladder
D009599:Nitroprusside; D002248:Carbon Monoxide; D006152:Cyclic GMP; D002118:Calcium