Effects of cAMP and cGMP on L-type calcium channel currents in rat mesenteric artery cells.
L-type Ca2+ channel currents in cultured rat mesenteric artery smooth muscle cells were recorded by the cell-attached patch-clamp technique. Depolarizing voltage steps from a holding potential of -40 mV elicited voltage-dependent inward Ba2+ currents. The inward currents were inhibited by nifedipine (10 microM) but enhanced by Bay K 8644 (5 microM), which suggests that the inward currents are carried almost exclusively by L-type Ca2+ channels. Application of dibutyryl cAMP (0.1-1 microM) and forskolin (0.01-1 microM) enhanced the activity of these Ca2+ channels. The dibutyryl cAMP induced enhancement of Ca2+ channels was antagonized by the serine/threonine kinase inhibitor H-8 (1 microM). Application of 8-bromo-cGMP (0.01-1 microM) and the cGMP inducer nitroglycerin (0.01-1 microM) inhibited the activity of these Ca2+ channels, and the inhibition of channel activity induced by 8-bromo-cGMP was antagonized by the serine/threonine kinase inhibitor H-8 (1 microM). These results suggest that in rat mesenteric artery cells, the L-type Ca2+ channel current is enhanced by a rise in intracellular cAMP levels and suppressed by a rise in intracellular cGMP levels. Furthermore, cGMP-induced Ca2+ channel inhibition may play a role in the expression of the nitric oxide-mediated vasodilating action of drugs such as nitroglycerin and atrial natriuretic peptide.
Taguchi
K
K
Department of Pharmacology, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Ueda
M
M
Kubo
T
T
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007546:Isoquinolines; D005576:Colforsin; C016276:8-bromocyclic GMP; D003994:Bucladesine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D005996:Nitroglycerin; D006152:Cyclic GMP; D009543:Nifedipine