Jpn. J. Pharmacol. 74 (2), 179-186 (1997)
Effects of cAMP and cGMP on L-Type Calcium Channel Currents in Rat Mesenteric
Artery Cells
Kyoji Taguchi, Masaki Ueda and Takao Kubo
Department of Pharmacology, Showa College of Pharmaceutical Sciences,
Machida, Tokyo 194, Japan
Abstract: 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.
Keywords: Ca+ channel, cAMP, cGMP, Mesenteric artery, Patch-clamp
Copyright© The Japanese Pharmacological Society 1997
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