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

Endothelin-1 (ET-1) and endothelin-3 (ET-3) induced a biphasic response (relaxation and contraction) in the guinea pig ileum. Short-term activation of protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu) inhibited the contractile but not the relaxing component of the responses, as did H-7. Long-term pretreatment with PDBu reversed the short-term inhibition but did not affect the tachyphylaxis induced by ET-1. These results suggest that PKC contributes to ET-1 contraction but not to tachyphylaxis. The ETA antagonist BQ-123, at 34 nM, competitively inhibited ET-1 contraction, but at 340 nM the inhibition was noncompetitive. Dose-response curves for ET-1 relaxation were shifted to the left. For ET-3, BQ-123 (340 nM) only decreased the maximal contractile response of the dose-response curve without affecting the relaxation. We suggest that in this tissue there is one receptor for ET-1-induced contraction, which is competitively antagonized by BQ-123, and another one for ET-3-induced contraction, which is noncompetitively antagonized by BQ-123.
J Cardiovasc Pharmacol 1993
PMID:Two receptor subtypes are involved in the contractile component of the guinea pig ileum responses to endothelins. 750 47

We studied the inhibitory effects of heparin, thrombin inhibitor, and protein kinase C (PKC) inhibitor on basal and thrombin-induced preproendothelin-1 (prepro-ET-1) and proto-oncogene c-fos mRNA expression in cultured bovine endothelial cells (ECs). Northern blot analysis using cDNA for bovine prepro-ET-1 as a probe showed that heparin lowered not only the basal but also the stimulated expression of prepro-ET-1 mRNA by thrombin. A selective thrombin inhibitor (argatroban) and a PKC inhibitor (staurosporine) also inhibited thrombin-induced but not basal prepro-ET-1 mRNA expression. Heparin similarly inhibited thrombin-induced c-fos proto-oncogene mRNA expression in ECs. These data suggest that heparin, in addition to its antithrombin effect, has an inhibitory effect on prepro-ET-1 mRNA expression, possibly via a PKC-dependent pathway.
J Cardiovasc Pharmacol 1993
PMID:Heparin inhibits endothelin-1 and proto-oncogene c-fos gene expression in cultured bovine endothelial cells. 750 97

The possible influence of an intracellular renin-angiotensin system (RAS) on control of cell communication in heart muscle was investigated in cell pairs isolated from adult rats. Junctional conductance (gj) was measured with two separated voltage-clamp circuits. Intracellular dialysis of angiotensin I (AI 10(-8) M) caused a decrease in gj of 76% (SE +/- 3.4) (p < 0.05) in 7 min. The effect of AI appears to be due mainly to its conversion to AII because enalaprilat (10(-9) M) dialysed into the cell caused an appreciable reduction in the effect of AI. AII (10(-8) M) alone caused a decrease in gj of 60% (SE +/- 3.8) (p < 0.05) in 45 s. The effect of AII on gj was suppressed by previous inhibition of protein kinase C (PKC), but enalaprilat could not alter the effect of the peptide. The results indicate that synthesis of AII inside cardiac myocytes plays an important role in modulation of gj and consequently on propagation of the electrical impulse in heart. The effect of AII on gj was blocked by DuP-753 (10(-9) M) administered intracellularly, whereas (Sar1Val5AlA8) AII also caused a slight decrease (1.97 +/- 0.07%) in gj. These findings indicate that an intracellular receptor is involved in the effect of the peptide on gj.
J Cardiovasc Pharmacol 1994 Apr
PMID:Is an intracellular renin-angiotensin system involved in control of cell communication in heart? 751 16

The cellular mechanisms by which dihydropyridine-type calcium antagonists lead to regression of hypertension-related cardiac hypertrophy have not been clarified. We previously showed that angiotensin II (AII) and endothelin-1 (ET-1) induce protein synthesis in isolated adult rat cardiomyocytes, probably through protein kinase C (PKC) as second messenger and the gene product of the early growth response gene-1 (Egr-1) as third messenger. We now show that the dihydropyridine derivative nisoldipine inhibits AII- and ET-1-induced protein synthesis at low concentrations (IC50 7.5 nM for 0.1 microM ET). Induction of c-fos and Egr-1 mRNA by AII and ET was completely blocked by nisoldipine. Therefore, nisoldipine may influence the signal transduction pathway, i.e., through PKC. These results provide a potential pressure-independent mechanism by which nisoldipine may influence development of cardiac hypertrophy.
J Cardiovasc Pharmacol 1994 Jul
PMID:Effects of nisoldipine on endothelin-1- and angiotensin II-induced immediate/early gene expression and protein synthesis in adult rat ventricular cardiomyocytes. 752 77

Effects of protein kinase C (PKC) activator and inhibitors on adrenal catecholamine release were examined in anesthetized dogs. Output of epinephrine (EPI) and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. All drugs were infused intraarterially (i.a.) into the adrenal gland through the phrenic abdominal artery. Infusion of the PKC activator phorbol-12,13-dibutyrate (PDB 0.1 micrograms/min) increased EPI and NE output during basal state and enhanced increases in catecholamine output induced by splanchnic nerve stimulation (SNS 1 and 3 Hz). These effects of PDB were abolished by the PKC inhibitor staurosporine (SSP 0.3 microgram/min), when both drugs were infused simultaneously. Infusion of SSP (0.1, 0.3, and 1 micrograms/min) caused a dose-dependent inhibition of the SNS-induced increases in EPI and NE output. SNS-induced increases in catecholamine output were also inhibited by another PKC inhibitor polymyxin B (PMB 0.1, 0.3, and 1 micrograms/min) and by the phospholipase C (PLC) inhibitor neomycin (NM 0.3, 1, and 3 mg/min). SSP, PMB, and NM did not affect basal output of EPI and NE. These results suggest that activation of PKC promotes release of adrenal catecholamines and provide indirect evidence that activation of PKC and PLC may be involved in SNS-induced release of catecholamines from dog adrenal gland.
J Cardiovasc Pharmacol 1994 Jul
PMID:Effects of protein kinase C activator and inhibitor on adrenal catecholamine release in response to splanchnic nerve stimulation in anesthetized dogs. 752 85

Recent electrophysiologic studies have provided evidence suggesting that as many as six different Cl- conductances can be identified in the sarcolemma of cardiac myocytes isolated from various animal species and areas of the heart. These include Cl- conductances activated by stimulation of protein kinase A, protein kinase C, extracellular ATP, intracellular Ca2+, membrane stretch, and a basally active Cl- conductance. Many basic biophysical and pharmacological properties of these channels are presently unknown, and the only molecular information presently available suggests that the cAMP-activated Cl- conductance is due to cardiac expression of an isoform of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel normally found in epithelial cells. We used the polymerase chain reaction (PCR) to amplify four distinct regions corresponding to the cardiac CFTR gene product from several cardiac tissues to determine if the molecular distribution of CFTR matches the distribution of cAMP-dependent Cl- channels in native myocytes. Amplification of regions corresponding to the first nucleotide binding domain (NBD1), transmembrane segments (TS) VII-XII, and the regulatory (R) domain showed a precise correlation to tissues that electrophysiologically exhibit sarcolemmal cAMP-dependent Cl- channels, whereas region TS I-VI exhibited a distribution independent of the presence of cAMP-dependent Cl- channels.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Electrophysiol 1995 Apr
PMID:A plethora of cardiac chloride conductances: molecular diversity or a related gene family. 754 94

We used various probes to examine the involvement of tyrosine kinases in norepinephrine (NE)-induced contractile responses of the isolated rat aorta denuded of endothelium. The putative tyrosine kinase inhibitors, genistein and tyrphostin, significantly inhibited the contractile responses of the aorta to NE but not to potassium chloride (KCl). The protein tyrosine phosphatase inhibitor, sodium orthovanadate, also selectively potentiated the contractile response of the artery to NE. The inhibitory effect of genistein on NE-induced contraction was observed both in the absence and presence of extracellular calcium, which produced phasic and tonic contractile responses, respectively. The effect of genistein was more pronounced on the phasic contraction, suggesting that tyrosine kinases play a greater role in mediating the responses associated with the release of intracellular calcium. Genistein, however, had no effect on contraction elicited by the direct protein kinase C (PKC) activator phorbol 12, 13 dibutyrate (PDB), providing evidence for the lack of involvement of tyrosine kinases in PKC-mediated contractile responses which contribute to the NE-induced tonic contraction. In contrast, genistein attenuated the contraction of the vessel evoked by the direct G-protein activator sodium fluoride (NaF), suggesting the involvement of tyrosine kinases in responses associated with G-protein activation. The data indicate that genistein- and tyrphostin-sensitive tyrosine kinases participate in NE-induced contraction of rat aortic smooth muscle. Although this may involve one or more steps in the signal transduction pathway, the enzymes appear to have a greater role in mediating the responses linked to the release of intracellular calcium and have no roles in certain other processes, including those mediated by PKC activation.
J Cardiovasc Pharmacol 1995 Jul
PMID:Role of tyrosine kinases in norepinephrine-induced contraction of vascular smooth muscle. 756 57

To examine the interaction of protein kinase C (PKC) with agonist-induced calcium fluxes in hypertension, cytosolic free calcium ([Ca2+]i) was measured in vascular smooth muscle cells (vSMC) of normotensive and spontaneously hypertensive rats (SHR) after incubation with phorbol,-12 myristate,-13 acetate (PMA) and application of angiotensin II (AII). To distinguish between calcium influx through voltage-dependent calcium channels and calcium mobilization from intracellular stores, the calcium agonist BayK 8644 was used. Resting [Ca2+]i was 108.0 +/- 10.6 nM (mean +/- SEM, n = 25) in normotensive and 102.0 +/- 11.4 nM (n = 21) in hypertensive cells. After pretreatment with PMA 10(-7) M for 60 min, resting [Ca2+]i of normotensive vSMC increased to 145.0 +/- 13.8 nM (n = 17) while the resting level of the hypertensive cells decreased to 68.0 +/- 2.4 nM (n = 14, p < 0.05 as compared with normotensive cells) in hypertensive vSMC. Maximum increase in [Ca2+]i induced with 10 M AII for normotensive and hypertensive vSMC was similar: 230.5 +/- 34.4 nM (n = 14) and 212.5 +/- 26.7 nM (n = 17). After pretreatment with PMA 10(-7) M, the maximum increase in [Ca2+]i induced by AII in hypertensive cells was limited to 108.0 +/- 6.2 nM (p < 0.05 as compared with normotensive cells), whereas the increase in [Ca2+]i in normotensive vSMC remained the same as before: 211.5 +/- 23.4 nM. After administration of 10(-5) M BayK 8644, [Ca2+]i increased by 54.3 +/- 12.2 nM (n = 4) and 43.4 +/- 17.4 nM (n = 5) in normotensive and hypertensive vSMC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1993 May
PMID:Angiotensin II responses after protein kinase C activation in vascular smooth muscle cells of spontaneously hypertensive rats. 768 44

The Na+/H+ exchanger in vascular smooth muscle cells represents a major mechanism for sodium influx and is also one of the principal mechanisms responsible for the regulation of intracellular pH (pHi). In this review, the relationship between pHi and vascular smooth muscle cell growth, the regulation of Na+/H+ exchange by vasoactive agents and growth factors, and the second messenger pathways that may be involved in activation of Na+/H+ exchange have been discussed. The exchanger appears to be important in vascular smooth muscle cell growth, based on results that (1) Na+/H+ exchange is stimulated by hypertrophic and hyperplastic agonists, (2) vascular smooth muscle cell proliferation is induced by cytoplasmic alkalinisation in the absence of mitogens, (3) vascular smooth muscle cell proliferation is dependent on extracellular sodium, and (4) inhibitors of Na+/H+ exchange block cell growth. Several pathways appear capable of activating the exchanger in vascular smooth muscle cells as there is evidence for both calcium and protein kinase C dependent and independent pathways. We speculate that the calcium and protein kinase C dependent pathways may play a role in the contractile response of differentiated vascular smooth muscle cells in the vessel wall, while the calcium and protein kinase C independent pathways may be involved in the proliferative response observed after arterial injury and in tissue culture.
Cardiovasc Res 1995 Feb
PMID:Regulation of sodium-hydrogen exchange in vascular smooth muscle. 773 91

We examined the effects of NIP-121, a potassium channel opener, on KCl- and norepinephrine (NE)-induced contraction, the phasic-contraction under the Ca(2+)-free condition and cytosolic free-Ca2+ mobilization using isolated rat aorta. NIP-121 as well as cromakalim inhibited, in the KCl- and NE-contractions concentration dependently. Glibenclamide, an ATP-sensitive potassium channel blocker, competitively reversed their inhibition. On the other hand, they did not inhibit the phasic-contractions induced by NE in Ca(2+)-free medium. In Fura-2-loaded rat aorta, NIP-121 inhibited only the late phase of the NE-induced cytosolic Ca2+ level ([Ca2+]cyt) increases that were inhibited by nicardipine. However, it did not inhibit the first [Ca2+]cyt increase, which was completely abolished by repeated applications of NE in Ca(2+)-free medium. Neither did it inhibit phorbol ester-induced contraction. The vasorelaxant mechanism of NIP-121 is attributable to the decrease in Ca2+ influx passing through the membrane Ca2+ permeable systems. In addition, inhibition of Ca2+ release from sarcoplasmic reticulum (SR) and of protein kinase C (PKC) activation may not be involved in vasorelaxation induced by NIP-121.
J Cardiovasc Pharmacol 1994 Dec
PMID:Inhibitory properties of NIP-121, a potassium channel opener, on high potassium- and norepinephrine-induced contraction and calcium mobilization in rat aorta. 789 70


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