Regulation by acetylcholine of Ca2+ current in rabbit atrioventricular node cells

1996 ◽  
Vol 271 (6) ◽  
pp. H2274-H2282 ◽  
Author(s):  
Y. Habuchi ◽  
M. Nishio ◽  
H. Tanaka ◽  
T. Yamamoto ◽  
L. L. Lu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Atrioventricular Node ◽  
Inhibitory Effect ◽  
Protein Kinase Inhibitor ◽  
Nitric Oxide Donor ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Type Iii ◽  
Dependent Protein

Effects of acetylcholine (ACh) on L-type Ca2+ current (ICa) were examined in isolated atrioventricular (AV) node cells exhibiting spontaneous contractions and pacemaker current (If). ACh at a saturating concentration of 10 microM reduced basal ICa by 48 +/- 6%. The ACh effect was abolished by dialysis with 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase inhibitor, or guanosine-5'-O-(2-thiodiphosphate). Dialysis with guanosine 3',5'-cyclic monophosphate (cGMP) or NG-monomethyl-L-arginine (L-NMMA) and application of the cGMP-dependent protein kinase inhibitor KT-5823 (1 microM) did not affect ACh inhibition of ICa. Nitric oxide donor 3-morpholinosydnonimine (100 microM) and type III phosphodiesterase (PDE) inhibitor trequinsin (10 nM) enhanced basal ICa by 10-20%, whereas type IV PDE inhibitor Ro-20-1724 (30 microM) together with trequinsin caused a large ICa stimulation comparable to that by 3-isobutyl-1-methylxanthine (IBMX). These findings indicate that ACh inhibits basal ICa primarily by suppressing cAMP synthesis and that these cells have a potent type III and IV PDE activity to determine the basal cAMP concentration. When ICa was stimulated by IBMX (100 microM), the inhibitory effect of ACh was slightly reduced by L-NMMA, cGMP, and methylene blue but not by KT-5823 or Ro-20-1724. ACh hardly inhibited, or even enhanced, IBMX-stimulated Ica when forskolin (3 microM) was coapplied or the IBMX concentration was increased to 500 microM. These findings suggest that cAMP is degraded in the presence of 100 microM IBMX to some extent. Type II PDE, for which IBMX has a relatively high inhibitor constant, seems to contribute partially to the cAMP degradation.

Nitric oxide donor SIN-1 inhibits mammalian cardiac calcium current through cGMP-dependent protein kinase

1995 ◽  
Vol 268 (1) ◽  
pp. C45-C54 ◽  
Author(s):  
G. M. Wahler ◽  
S. J. Dollinger
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Calcium Current ◽  
Inhibitory Effect ◽  
Cardiac Cells ◽  
Nitric Oxide Donor ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

The effect of the nitric oxide (NO) donor SIN-1 (3-morpholino-sydnonimine) on the calcium current (ICa) was examined in guinea pig ventricular myocytes. SIN-1 had little effect on basal ICa. After moderate stimulation of ICa with 10 nM isoproterenol (ISO), 10 microM SIN-1 caused either stimulation or inhibition of ICa; 100 microM SIN-1 consistently caused inhibition. SIN-1 (1-100 microM) inhibited ICa equally following considerable enhancement of ICa by either 1 microM ISO or 100 microM 3-isobutyl-1-methylxanthine, a nonspecific phosphodiesterase (PDE) inhibitor. SIN-1 (100 microM) also inhibited ICa equally following enhancement by either 10 microM pipette adenosine 3',5'-cyclic monophosphate (cAMP) or hydrolysis-resistant 8-bromo-cAMP. Thus the inhibitory effect of SIN-1 appears independent of PDEs. Addition of LY-83583 (a blocker of guanylate cyclase) to the pipette or superfusion with KT-5823 [a blocker of the guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase] suppressed the inhibitory effect of SIN-1. We conclude that NO is an important modulator of beta-adrenergic effects on ICa and that the mechanism of NO inhibition of ICa in mammalian cardiac cells involves the cGMP-dependent protein kinase.

A novel 5-HT1-like receptor subtype mediates cAMP synthesis in porcine pial vein

1995 ◽  
Vol 268 (4) ◽  
pp. H1383-H1389 ◽  
Author(s):  
M. Ueno ◽  
T. Ishine ◽  
T. J. Lee
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Phosphodiesterase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Dependent Protein ◽  
Ics 205 930

The 5-hydroxytryptamine (5-HT) receptor subtype mediating 5-HT inhibition of spontaneous rhythmic contractions (SRC) in the porcine pial vein was characterized. Results from pharmacological studies using in vitro tissue bath techniques indicated that the inhibitory effects of 5-HT on SRC were qualitatively and quantitatively mimicked by 5-HT1-like agonists 5-methoxytryptamine (5-MT) and 5-carboxamidotryptamine (5-CT). 5-HT-, 5-MT-, and 5-CT-induced inhibitions of SRC were attenuated in a concentration-dependent manner by methysergide, which yielded similar pA2 values against these three agonists, suggesting that 5-HT, 5-MT, and 5-CT act on the same 5-HT1-like receptors. 5-MT inhibition of SRC was not affected by blocking 5-HT2 (with ketanserin and spiperone), 5-HT3 (with MDL-72222 and ICS-205-930), or 5-HT4 (with ICS-205-930) receptors. Neither was 5-MT inhibition of SRC affected by blocking 5-HT1A (with propranolol and spiperone), 5-HT1B (with propranolol), or 5-HT1C (with ketanserin) receptors. Furthermore, 5-HT and 5-MT inhibitions of SRC were enhanced by cilostazol [a selective adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor] and were diminished by KT-5720 (a cAMP-dependent protein kinase inhibitor) but were not affected by M&B-22948 [a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor] or KT-5823 (a cGMP-dependent protein kinase inhibitor). Biochemical studies further demonstrated that 5-HT inhibition of SRC in porcine pial veins was accompanied by an increase in cAMP, but not cGMP, synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of the proteins of the intestinal Na(+)-K(+)-2Cl- cotransporter

1994 ◽  
Vol 267 (2) ◽  
pp. C375-C384 ◽  
Author(s):  
W. Suvitayavat ◽  
P. B. Dunham ◽  
M. Haas ◽  
M. C. Rao
Keyword(s):  
Protein Kinase ◽  
Subcellular Fractionation ◽  
Inhibitory Effect ◽  
Polyclonal Antiserum ◽  
Calyculin A ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Microsomal Membranes ◽  
Dependent Protein

Absorptive intestinal epithelia, such as that of the winter flounder, absorb salt via a bumetanide-sensitive Na(+)-K(+)-2Cl- cotransport mechanism on the brush-border membrane (BBM). The present study demonstrates the first molecular characterization of the intestinal Na(+)-K(+)-2Cl- cotransporter and its unique regulation. The photoaffinity bumetanide analogue, 4-[3H]benzoyl-5-sulfamoyl-3- (3-thenyloxy)benzoic acid, specifically labeled three groups of proteins in flounder intestinal microsomal membranes (MM): a approximately 180-kDa peptide, prominently labeled, and diffuse bands at approximately 110-70 and 50 kDa, less intensely labeled. Subcellular fractionation revealed a single prominently labeled protein of approximately 170 kDa in BBM but not in basolateral membranes (BLM) and little or no labeling of proteins of approximately 110-70 or 50 kDa. Polyclonal antiserum raised against the Ehrlich ascites cell cotransporter identified a 180-kDa peptide in MM and a 175-kDa peptide (pI approximately 5.4) in BBM but none in BLM or in the cytosol of flounder intestine. As predicted from the regulation of cotransport in this tissue, phosphorylation of this protein is increased by guanosine 3',5'-cyclic monophosphate (cGMP)-dependent but not by adenosine 3',5'-cyclic monophosphate-dependent protein kinase. In addition, phosphorylation of the protein is not increased by protein kinase C or Ca2+/calmodulin-dependent protein kinase but is increased by the phosphatase inhibitor calyculin A. Finally, calyculin A preserves the inhibitory effect of cGMP on ion transport, even in the absence of the nucleotide, suggesting that phosphorylation-dephosphorylation mechanisms are crucial in cotransporter regulation. Thus the flounder intestinal cotransporter is a approximately 175-kDa BBM protein that can be regulated by phosphorylation.

scholarly journals A Novel Calcium-Dependent Protein Kinase Inhibitor as a Lead Compound for Treating Cryptosporidiosis

2013 ◽  
Vol 208 (8) ◽  
pp. 1342-1348 ◽  
Author(s):  
Alejandro Castellanos-Gonzalez ◽  
A. Clinton White ◽  
Kayode K. Ojo ◽  
Rama S. R. Vidadala ◽  
Zhongsheng Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Lead Compound ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase

Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor, NU7441

2013 ◽  
Vol 53 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Ales Tichy ◽  
Kamila Durisova ◽  
Barbora Salovska ◽  
Jaroslav Pejchal ◽  
Lenka Zarybnicka ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Dependent Protein Kinase ◽  
Dependent Protein
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