Urotensin-II Receptor Stimulation of Cardiac L-type Ca2+Channels Requires the βγ Subunits of Gi/o-protein and Phosphatidylinositol 3-Kinase-dependent Protein Kinase C β1 Isoform

We examined the possibility that, in addition to stimulation of guanylate cyclase (GC), atrial natriuretic peptide (ANP) also activates phospholipase C (PLC) in cultured rat inner medullary collecting tubule (RIMCT) cells. ANP (10(-12)M) causes marked release of inositol trisphosphate (IP3) at a concentration that does not stimulate GC. Concentrations of ANP that stimulate GC (greater than or equal to 10(-10) M) result in attenuated IP3 release. Similarly, exogenous dibutyryl guanosine 3',5'-cyclic monophosphate (10(-6) M) markedly inhibits the response to 10(-10) M ANP. Inhibition of cyclic nucleotide-dependent protein kinase by H 8, but not inhibition of protein kinase C by H 7, restores the response to 10(-8) and 10(-6) M ANP. Therefore, activation of cyclic nucleotide-dependent protein kinase inhibits ANP-stimulated PLC activity. Activation of protein kinase C by phorbol 12-myristate-13-acetate (PMA) decreases ANP-stimulated IP3 production. Pretreatment with H 7, but not H 8, prevents inhibition by PMA. To explore a potential role for G proteins, we examined the effect of guanine nucleotide analogues on ANP-stimulated IP3 production in saponin-permeabilized cells. ANP-stimulated IP3 production is enhanced by GTP gamma S and is inhibited by GDP beta S. Similarly, preincubation with pertussis toxin prevents ANP-stimulated IP3 release. We conclude that ANP stimulates PLC in RIMCT cells via a pertussis toxin-sensitive G protein. Stimulation of PLC is inhibited on activation of either cyclic nucleotide or Ca2+-phospholipid dependent protein kinases.

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Involvement of Ca2+/calmodulin-dependent protein kinase II in the activation of carnitine palmitoyltransferase I by okadaic acid in rat hepatocytes

Biochemical Journal ◽

10.1042/bj3210211 ◽

1997 ◽

Vol 321 (1) ◽

pp. 211-216 ◽

Cited By ~ 11

Author(s):

Guillermo VELASCO ◽

Manuel GUZMÁN ◽

Victor A. ZAMMIT ◽

Math J. H. GEELEN

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Specific Inhibitor ◽

Rat Hepatocytes ◽

Dependent Protein Kinase ◽

Kinase C ◽

Dependent Protein ◽

Carnitine Palmitoyltransferase I ◽

Cpt I ◽

Stimulation Of

The present work was undertaken to study the mechanism by which okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, stimulates carnitine palmitoyltransferase I (CPT-I) in isolated rat hepatocytes [Guzmán, Kolodziej, Caldwell, Costorphine and Zammit (1994) Biochem. J. 300, 693–699]. The OA-induced stimulation of CPT-I was abolished by the general protein kinase inhibitor K-252a as well as by KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (Ca2+/CM-PKII). However, neither the protein kinase C-specific inhibitor bisindolylmaleimide nor the protein kinase A/protein kinase C inhibitor H-7 was able to prevent the OA-induced stimulation of CPT-I. Hepatocyte-shrinkage-induced stimulation of CPT-I as well as OA-induced hepatocyte shrinkage was prevented by KN-62. KN-62 also antagonized the OA-enhanced release of lactate dehydrogenase from digitonin-permeabilized hepatocytes. Exposure of 32P-labelled hepatocytes to OA increased the degree of phosphorylation of Ca2+/CM-PKII, as immunoprecipitated by a monoclonal antibody raised against the α-subunit of rat brain kinase. This effect of OA was also antagonized by KN-62. The results thus indicate that the OA-dependent stimulation of CPT-I may be mediated (at least in part) by increased phosphorylation and subsequent activation of Ca2+/CM-PKII.

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Evidence for Involvement of Protein Kinase C and Cyclic Adenosine 3’,5’ Monophosphate-Dependent Protein Kinase in the 1,25-Dihydroxy-Vitamin D3-Mediated Rapid Stimulation of Intestinal Calcium Transport, (Tr anscaltachia)*

Endocrinology ◽

10.1210/endo-127-1-39 ◽

1990 ◽

Vol 127 (1) ◽

pp. 39-45 ◽

Cited By ~ 81

Author(s):

ANA R. DE BOLAND ◽

ANTHONY NORMAN

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Vitamin D3 ◽

Calcium Transport ◽

Dependent Protein Kinase ◽

Kinase C ◽

Dependent Protein ◽

Rapid Stimulation ◽

1,25 Dihydroxy Vitamin D3 ◽

Stimulation Of

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Distinct voltage-dependent regulation of a heart-delayed IK by protein kinases A and C

AJP Cell Physiology ◽

10.1152/ajpcell.1991.261.6.c1081 ◽

1991 ◽

Vol 261 (6) ◽

pp. C1081-C1090 ◽

Cited By ~ 72

Author(s):

K. B. Walsh ◽

R. S. Kass

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Protein Kinase A ◽

Dependent Protein Kinase ◽

Kinase C ◽

Voltage Dependent ◽

Dependent Protein ◽

Kinetics Of ◽

Kinase A ◽

Stimulation Of

We have investigated the effects of stimulation of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (protein kinase A) and Ca(2+)-diacylglycerol-dependent protein kinase (protein kinase C) on the delayed rectifier K+ current (IK) in guinea pig ventricular cells using a whole cell arrangement of the patch-clamp procedure. Stimulation of either protein kinase C or A resulted in enhanced IK activity. Augmentation of IK observed during stimulation of protein kinase A occurred in a markedly voltage-dependent manner, with the largest increases occurring at potentials near the threshold for IK activation. Enhancement of IK during stimulation of protein kinase C followed a different pattern, with minimal effects of the enzyme near IK threshold. Neither protein kinase A nor C altered the kinetics of IK activation, although both kinases slightly changed the kinetics of deactivation. Both kinases increased IK maximal conductance, but the effects of each kinase on the voltage-dependence of activation differed. Protein kinase A shifted IK activation toward more negative voltages but did not affect the slope of the activation curve. Protein kinase C, in contrast, changed the slope of the IK activation curve, with only a small effect on the half-maximal voltage of activation. These contrasting effects on the voltage dependence of IK activation are consistent with actions of the kinases at distinct sites on or near the IK channel protein.

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