Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of protein tyrosine kinases (PTK) on L-type calcium channels in cultured retinal pigmented epithelium (RPE) from rats with retinal dystrophy was investigated. Barium currents through Bay K 8644 (10(-6) M) sensitive L-type channels were measured using the patch-clamp technique. The current density of L-type currents is twice as high and the inactivation time constants are much slower than in cells from nondystrophic control rats. Application of the PTK blockers genistein, lavendustin A, and herbimycin A (all 5 x 10(-6) M) led to an increase of L-type currents. Intracellular application of pp60c-src (30 U/ml) via the patch pipette led to a transient decrease of L-type currents. The protein kinase A (PKA) and PKG blocker H9 (10(-6) M) showed no effect on L-type currents. However, the protein kinase C blocker chelerythrine (10(-5) M) reduced these currents. Up-regulation of PKC by 10(-6) M 4beta-phorbol-12 myristate-13 acetate (PMA) led to a decrease of L-type currents. Additional application of genistein led to a further decrease of these currents. However, intracellular application of pp60(c-src) in PMA-treated cells led to a transient increase of L-type currents. Investigating the calcium response to bFGF application showed that RPE cells from RCS rats used different pathways than control RPE cells to increase cytosolic free calcium. This different pathway does not involve the activation of L-type channels. The present study with RPE cells from rats with retinal dystrophy shows a changed integration of PTK and PKC in channel regulation. Considering the altered response to bFGF in RCS-RPE cells, this disturbed regulation of L-type channels by tyrosine kinases is involved in the etiology of retinal degeneration in RCS rats.
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PMID:Altered regulation of L-type channels by protein kinase C and protein tyrosine kinases as a pathophysiologic effect in retinal degeneration. 973 15

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.
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PMID:Inhibitory effect of C-type natriuretic peptide on L-type calcium channel currents in gastric antral myocytes of guinea pigs. 1735 30

Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, relaxes gastrointestinal smooth muscle. L-type calcium channel currents play an important role in regulating smooth muscle contraction. The effect of DNP on L-type calcium channel currents in gastrointestinal tract is still unclear. This study was designed to investigate the effect of DNP on barium current (I(Ba)) through the L-type calcium channel in gastric antral myocytes of guinea pigs and cGMP-pathway mechanism. The whole-cell patch-clamp technique was used to record L-type calcium channel currents. The content of cGMP in guinea pig gastric antral smooth muscle and perfusion solution was measured using radioimmunoassay. DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in perfusion medium. DNP concentration-dependently inhibited I(Ba) in freshly isolated guinea pig gastric antral circular smooth muscle cells (SMCs) of guinea pigs. DNP-induced inhibition of I(Ba) was partially blocked by LY83583, an inhibitor of guanylate cyclase. KT5823, a cGMP-dependent protein kinase (PKG) inhibitor, almost completely blocked DNP-induced inhibition of I(Ba). However, DNP-induced inhibition of I(Ba) was potentiated by zaprinast, an inhibitor of cGMP-sensitive phosphodiesterase. Taken together, DNP inhibits L-type calcium channel currents via pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs.
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PMID:Effect of dendroaspis natriuretic peptide (DNP) on L-type calcium channel current and its pathway. 2059 55

This study was designed to elucidate high-K(+)induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high K(+) (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high K(+) (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high K(+)-induced relaxation. K(+) channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium (Ba(2+)) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent K(+) channel (K(V)) blocker, inhibited high K(+)-induced relaxation, hence reversing to tonic contraction. High K(+)-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and K(V) channel blocker sensitive high K(+)-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high K(+)-induced relaxation which was activated by NO/sGC pathway and by K(V) channel dependent mechanism.
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PMID:Nitric Oxide-mediated Relaxation by High K in Human Gastric Longitudinal Smooth Muscle. 2235 79