Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of dopamine on depolarization-induced Ca2+ influx was studied using the fluorescent Ca2+ indicator fura-2 in synaptic terminals of bipolar neurons from gold-fish retina. Dopamine reversibly enhanced the rise in intracellular Ca2+ elicited by elevated external potassium. The enhancement was slowly reversible. The effect of dopamine was mimicked by forskolin and CPT-cAMP, a membrane-permeant analog of cAMP. However, 1,9-dideoxyforskolin, a forskolin analog that does not activate adenylyl cyclase, was ineffective. This suggests that dopamine, via cAMP, regulates the rise in presynaptic Ca2+ concentration in response to depolarization, potentially enhancing transmitter release.
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PMID:Dopamine enhances Ca2+ responses in synaptic terminals of retinal bipolar neurons. 819 49

Dopamine receptors are present in the medullary thick ascending limb (mTAL) of Henle, but their effect on ion transport in this nephron segment has not been tested. Therefore, we studied the short-term effects of dopamine on Na(+)-K(+)-2Cl- cotransport (assessed by 100 microM bumetanide-sensitive 86Rb uptake) in rat mTAL tubular suspensions. Dopamine (1 microM) stimulated bumetanide-sensitive 86Rb uptake (72.1 +/- 10.6% vs. control, n = 5) by increasing total 86Rb uptake and by decreasing bumetanide-insensitive 86Rb uptake; this effect was concentration dependent. The dopamine-induced stimulation of Na(+)-K(+)-2Cl- cotransport activity was mimicked by calyculin A, a protein phosphatase (PP) inhibitor, and Sp isomer of adenosine 3',5'-cyclic monophosphothioate (Sp-cAMP[S]), a protein kinase A (PKA) agonist, and blocked by Rp isomer of 8-(4-chlorophenylthio)-cAMP[S] (Rp-8-CPT-cAMP[S]), a PKA inhibitor (n = 5). Dopamine did not increase the stimulatory effect of the PP inhibitor. However, the stimulatory effect of the PP inhibitor and PKA agonist was additive and approached the stimulatory effect of dopamine. The stimulatory effects of dopamine, PP inhibitor, and PKA agonist persisted even when intracellular sodium was clamped by 5 microM monensin. When K+ channels were blocked by 1 mM BaCl2, the effects of dopamine and calyculin A on the cotransport were no longer apparent, although the stimulatory effect of the PKA agonist was attenuated. We conclude that dopamine stimulates Na(+)-K(+)-2Cl- cotransport activity. This action is mediated mainly by PKA-dependent phosphorylation/dephosphorylation processes and modulated by dopamine actions on K+ channels.
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PMID:Stimulation of Na(+)-K(+)-2Cl- cotransport in rat medullary thick ascending limb by dopamine. 899 53

The mechanism(s) by which dopamine inhibits Na+-K+-ATPase activity in the renal proximal tubule is still controversial. We studied the short-term effects of dopamine on the sodium pump in rat renal proximal tubule suspensions with the 86Rb uptake method. Dopamine and the D1-like agonist, SKF81297, initially stimulated Na+-K+-ATPase activity at 5 min and subsequently inhibited it at 10 min and 20 min; the inhibition by 10 microM dopamine at 20 min was 21.3 +/- 4.5%. The inhibitory effect of dopamine on Na+-K+-ATPase activity was mimicked by thymeleatoxin (a classical protein kinase C [PKC] agonist) while Sp-8-CPT-cAMPS (a protein kinase A [PKA] agonist) had no effect. However, the combination of the PKC and PKA agonists mimicked the biphasic effects of dopamine and SKF81297. Rp-8-CPT-cAMPS (a PKA inhibitor), U-73122 (a phospholipase C inhibitor), or calphostin C (a PKC inhibitor), blocked the dopamine-mediated biphasic effects on Na+-K+-ATPase activity. It is suggested that the biphasic effects of dopamine on Na+-K+-ATPase activity (an initial stimulation and a subsequent inhibition) are transduced by activating both PKA and PKC through a D1-like receptor.
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PMID:Biphasic effects of dopamine on 86rubidium uptake in rat renal proximal tubules. 1080 34

Pigmented (PE) and nonpigmented (NPE) ciliary epithelial cells comprise the ciliary epithelium, the site of aqueous humor formation in the eye. In man, catecholamines increase the rate of aqueous humor formation, but the mechanism underlying these effects is not understood. Recent evidence suggests that Na-K-Cl cotransport plays a central role in blood-to-aqueous chloride transport across ciliary epithelium in cow and rabbit. We therefore investigated whether catecholamines stimulate Na-K-Cl cotransport in human PE cells. Na-K-Cl cotransporter protein was detected as a 170 kDa protein band on immunoblots. Immunofluorescence microscopy detected cotransporter on the basolateral membranes of the PE layer of ciliary epithelium from a human donor. Cotransporter immunofluorescence was also detected in cultured PE cells. Na-K-Cl cotransport activity measured as ouabain-insensitive bumetanide-sensitive(86)Rb uptake was stimulated by isoproterenol 1.6-fold, with an EC(50) = 28 n M and maximal stimulation at 1 microM. Other transport mechanisms involved in(86)Rb uptake were not affected. Stimulation by 1 microM isoproterenol was blocked by 10 n M ICI 118,551, a beta(2)-specific receptor antagonist, whereas the receptor subtype-specific antagonists yohimbine (alpha(2)), prazosin (alpha(1)) and atenolol (beta(1)) were ineffective. Norepinephrine stimulation (EC(50) = 280 n M) was also blocked by ICI 118,551. Dopamine stimulated Na-K-Cl cotransport 1.6-fold with an EC(50) = 14 microM. The dopamine effect could not be blocked by 10 microM SCH 23390, a D1-antagonist, but was abolished by ICI 118,551. Forskolin and CPT-cAMP stimulated Na-K-Cl cotransport 1.79- and 1.71-fold, respectively, whereas the inactive forskolin analogue 1,9-dideoxyforskolin had no effect. However, high concentrations of the PKA inhibitors PKI amide 14-22 and KT 5720 were needed to inhibit both PKA activity in cell lysates and isoproterenol stimulation of cotransport. This finding may indicate the presence of a novel PKA isoform in PE cells. Inhibitors of other protein kinases, including myosin light chain kinase, protein kinase G, calmodulin-dependent kinase and tyrosine kinase, were without effect on stimulated Na-K-Cl cotransport. When EC(50)s for catecholaminergic stimulations of Na-K-Cl cotransport in PE were compared to those in NPE, values within five-fold of one another were seen for isoproterenol and norepinephrine. In contrast, dopamine was 28-fold more potent in NPE than in PE. The data suggest that both PE and NPE possess beta(2)adrenergic receptors, but only NPE cells possess dopamine D1 receptors linked to Na-K-Cl cotransport.
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PMID:Catecholaminergic regulation of Na-K-Cl cotransport in pigmented ciliary epithelium: differences between PE and NPE. 1113 77

Dopamine neurotransmission influences those cognitive processes, which are generally regarded as prefrontal cortical functions. In previous positron-emission-tomography (PET) studies, net blood-brain clearance of [18F]-fluoro-l-DOPA (FDOPA) correlated with impaired cognitive performance in patients with Parkinson's disease or schizophrenia. We hypothesized that FDOPA influx also correlates with performance of cognitive tasks associated with prefrontal functioning in healthy volunteers. The net blood-brain clearance of FDOPA (K(in)(app)) was mapped in a group of 11 healthy volunteers and calculated in striatal volumes-of-interest. The Wisconsin-Card-Sorting-Test (WCST), Stroop-Test, Trail-Making-Test (TMT-A/B), and Continuous-Performance-Test (CPT-M) had been administered previously to the same subjects. No correlation of K(in) (app) with perseverative errors in WCST or age could be found. However, there were significant positive correlations between the magnitude of K(in)(app) in caudate nucleus, putamen, and midbrain with performance of the TMT-B, CPT-M, and the Stroop test. Highest correlations were found between the time needed to perform the Stroop interference task and the K(in)(app) of striatal areas (Caudate nucleus: -0.780, P = 0.005; putamen: -0.870, P < 0. 001). Thus, the present findings reveal a strong correlation between dopamine synthesis capacity in striatum of healthy volunteers and performance of cognitive tasks linked to the prefrontal cortex.
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PMID:'Prefrontal' cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: an exploratory [18F]-fluoro-L-DOPA-PET investigation. 1713 2