Inhibitory effect of C-type natriuretic peptide on L-type calcium channel currents in gastric antral myocytes of guinea pigs.
The role of C-type natriuretic peptide (CNP) in the gastrointestinal tract is still unclear. This study was designed to investigate the effect of CNP on barium current (I(Ba)) through the L-type calcium channel in gastric antral myocytes of guinea pigs. The whole-cell patch clamp technique was performed in gastric antral myocytes isolated by collagenase in guinea pigs. CNP significantly inhibited I(Ba) in a dose-dependent manner at the concentrations of 0.001, 0.01, and 0.1 micromol/l, CNP inhibited I(Ba) to 81.56 +/- 2.48 %, 73.64 +/- 3.65 %, and 57.77 +/- 4.93 % of control at 0 mV, respectively. The values of steady-state half-inactivation voltage (33.6 +/- 2.6 mV and 33.8 +/- 3.4 mV, in control and CNP groups, respectively) or the half-activation voltage (-12.6 +/- 2.2 mV and 12.4 +/- 1.8 mV) of I(Ba) were not significantly changed (p > 0.05, n = 6). 8-br-cGMP (1 mmol/l) mimicked the effect of CNP on I(Ba), and the peak current of I(Ba) was inhibited from -403.84 +/- 61.87 pA to 318.94 +/- 67.17 pA (p < 0.05, n = 5). In the presence of LY83583 (0.1 micromol/l), a nonspecific inhibitor of guanylate cyclase, CNP (0.1 micromol/l)-induced inhibition of I(Ba) was partially blocked (n = 13, p < 0.05 ). However, when the cell was pretreated with zaprinast (0.1 micromol/l), an inhibitor of cyclic guanosine monophosphate (cGMP) sensitive phosphoesterase, the inhibitory effect of CNP on I(Ba) was significantly potentiated (n = 11, p < 0.05). KT5823 (1 micromol/l), a cGMP-dependent protein kinase (PKG) inhibitor, almost completely blocked CNP-induced inhibition of I(Ba). The results suggested that CNP can inhibit L-type calcium channel currents, and the inhibitory effect is mediated by pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs.
Sun
J B
JB
Department of Physiology, Medical College, Shanghai Jiaotong University, Shanghai, China.
Huang
X
X
Xu
H Y
HY
Li
X L
XL
Gao
L
L
Kim
Y C
YC
Xu
W X
WX
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage*; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020098:Natriuretic Peptide, C-Type