Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In SH-SY5Y human neuroblastoma cells, addition of acetylcholine or carbachol rapidly induces a transient protrusion of lamellipodia. The protrusions appear after a delay of 30 sec and persist for a period of about 5 min at the margins of cell somata and at the distal parts of cell processes. They are caused by a strikingly increased, cytochalasin B-sensitive assembly of actin at the cell periphery. They often detach from the substrate, retracting and protruding again. In retinoic acid-induced neuronally differentiated cells, this initialized protrusive activity is restricted to growth cones. d-Tubocurarine does not influence, but atropine totally inhibits the cholinergic induction of the actin-driven protrusions, suggesting that a muscarinic receptor-mediated activation of the phosphoinositol signaling pathway is involved. Depolarization by increase of the potassium concentration and ionophore-mediated Ca(2+)-influx are ineffective to trigger the protrusive and ruffling activity. An identical cytochalasin B-sensitive actin-driven response is caused by treating of the cells with the protein kinase C (PKC) activator 12-myristate-13-acetate. In this case, however, lamellar protrusions are formed after a delay of at least 3 min and are maintained for several days. Incubating the cells with the protein kinase C inhibitor bisindolylmaleide or staurosporine inhibits both the muscarinic receptor-mediated and phorbolester-mediated actin-driven response, suggesting that activated PKC plays a crucial role.
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PMID:Muscarinic receptor-mediated induction of actin-driven lamellar protrusions in neuroblastoma cell somata and growth cones. Involvement of protein kinase C. 765 99

The modulation of ACh on delayed rectifier-like potassium currents (I(K)) was studied in freshly dissociated cerebral cortical neurons using the whole-cell patch-clamp technique. Wistar rats between 10- and 14-day old of both sexes were used. After rats were decapitated, their brains were quickly removed, iced, and then manually cut into 400 mum slices. Slices were then incubated for 0.5 h at 32 degrees C in a buffered artificial cerebrospinal fluid (ACSF) bubbled with 95% O2, 5% CO2. Slices were then removed into buffered ACSF containing protease (0.5 mg/ml) at 32 degrees C. After 30 min of enzyme digestion, tissue was rinsed three times in the buffered saline. Then the enzyme-treated slices were mechanically dissociated with a graded series of fire-polished Pasteur pipettes. The cell suspension was then plated into a 35 mm dish and placed on the stage of a Olympus inverted microscope. For whole-cell recordings of currents, standard voltage-clamp techniques were used. Neurons were held at -80 mV, and the I(K) was evoked by 2 000 ms depolarizing voltage commands to potential between -40 mV and +60 mV in 10 mV steps applied at a frequency of 0.5 Hz. It was found that the inhibitory effect of ACh (0.1, 1, 10, 100 mumol/L) on I(K) was dose-dependent. It was also found that ACh affected the activation process of I(K) significantly, i.e., the activation curve of I(K) was characterized by half-activation potential of (-41.8+/-9.7) mV and a slope factor of (30.7+/-7.2) mV in the cortical neurons and they were changed to (-122.4+/-38.6) mV and (42.4+/-7.0) mV, respectively, after giving ACh (10 mumol/L). Tubocurarine (100 mumol/L) antagonized the inhibitory effect of ACh on I(K), and the drop of currents varied from the control value of (36.5+/-7..8)% to (16.9+/-13.8)% (n=8, P<0.01). 4-DAMP (10 mumol/L) blocked the inhibitory effect of ACh on I(K), and the currents reduced from the control value of (36.5+/-7.8)% to (26.8+/-4.7) % (n=6, P<0.05). Pirenzepin did not antagonize the inhibition of ACh on I(K) (n=7, P>0.05). Chelerythrine (20 mumol/L) blocked the inhibitory effect of ACh on I(K) and the currents reduced from the control value of (36.5+/-7.8)% to (11.7+/-17.3)% (n=6, P<0.05). On the contrary, PDBu (10 mumol/L) strengthened the inhibition of ACh on I(K) and the drop of currents changed from the control value of (36.5+/-7.8)% to (59.2+/-14.0)% (n=5, P<0.05). PDBu abolished the antagonism of chelerythrine on ACh in cortical neurons. It is suggested that the ACh-induced depolarization of neurons in the cortex is attributed to the inhibition of I(K) that is most likely evoked by the activation of nicotinic ACh receptors and muscarinic M3 receptor via protein kinase C (PKC) signal transduction pathway.
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PMID:[Inhibition of ACh on the delayed rectifier-like potassium current in acutely isolated cerebral cortical neurons of rats]. 1648 5