α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture

Levine, Lawrence; Moskowitz, Michael A.

doi:10.1073/pnas.76.12.6632

Cited by 61 publications

(19 citation statements)

References 21 publications

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“…Evidence for increased synthesis of renal prostaglandins has also been obtained in several conditions in which there is increased activity of renin-angiotensin system: hemorrhage (9), renal artery stenosis (35), cirrhosis with ascites (46) and Bartter's syndrome (46). Intrarenal infusions of norepinephrine and renal nerve stimulation (5) also enhance the release of PGE-like substances from the kidney and norepinephrine stimulates prostaglandin synthesis is isolated canine kidney cells (47). Whether other hormones, known to stimulate PGE2 synthesis (antidiuretic hormone and bradykinin) also contribute to enhanced prostaglandin synthesis in the sodium-depleted animals is not known.…”

Section: Discussionmentioning

confidence: 99%

Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog.

Oliver¹,

Pinto²,

Sciacca³

et al. 1980

J. Clin. Invest.

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A B S T R A C T To determine whether vasoactive renal hormones modulate renal blood flow during alterations of sodium balance, simultaneous measurements of arterial and renal venous concentrations of norepinephrine and prostaglandin E2 (PGE2) and of plasma renin activity, as well as renal blood flow and systemic hemodynamics were carried out in 24 sodiumdepleted and 28 sodium-replete anesthetized dogs. The mean arterial blood pressure of the sodium depleted dogs was not significantly different from that of the animals fed a normal sodium diet, but cardiac outptut was significantly lower (3.07±0.18 vs. 3.77±0.17 liters/mim, mean±SEM; P < 0.01). Despite the higher total peripheral vascular resistance in the sodiumdepleted dogs (46.1±2.9 vs. 37.0±2.1 arbitrary resistance U; P < 0.02), the renal blood flow and renal vascular resistance were not significantly different in the two groups. The arterial plasma renin activity and concentration of norepinephrine were higher in the sodium-depleted animals than in the controls; the arterial concentration of PGE2 was e(ual in both groups. The renal venous plasma renin activity was higher in the sodium-depleted dogs. Similarly, the renal venous norepinephrine concentration was higher in the sodium-depleted dogs than in the controls (457±44 vs. 196±25 pg/ml; P <0.01); renal venous PGE2 concentration was also higher in the sodium depleted dogs (92±22 vs. 48±11 pg/ml; P < 0.01). Administration of indomethacin to five sodium-replete dogs had no effect on renal blood flow. In five sodium-depleted dogs indomethacin lowered renal blood flow from 243±19 to 189+30 ml/min (P < 0.05) and PGE2 in renal venous blood from 71±14 to 15±2 pg/ml (P < 0.02). The results indicate that moderate chronic sodium depletion, in addition to enhancing the activity of the renin-angiotensin system, also increases the activity of the renal adrenergic nervous system and increases renal PGE2 synthesis. In sodiumReceived for publication 19 February 1980 and in revised form 4 June 1980. 748 depleted dogs, inhibition of prostaglandin synthesis was associated with a significant decrease in renal blood flow. The results suggest that the renal blood flow is maintained during moderate sodiulm depletion by an effect of the prostaglandins to oppose the vasoconstrictor effects of angiotensin II and the rencal sympathetic nervous system.

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Section: Discussionmentioning

confidence: 99%

Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog.

Oliver¹,

Pinto²,

Sciacca³

et al. 1980

J. Clin. Invest.

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“…Angiotensin II stimulates PGE2 synthesis in in vitro conditions in endothelial (35) vascular smooth muscle (36) and renal interstitial (37) cells, and intrarenal infusions of angiotensin II cause increased biosynthesis of PGE2 in the kidney (32). Similarly, intrarenal infusions of norepinephrine and renal nerve stimulation (38) enhance the release of PGE-like substances from the kidney and norepinephrine stimulates prostaglandin synthesis in isolated canine kidney cells (39).…”

Section: Resultsmentioning

confidence: 99%

Participation of the Prostaglandins in the Control of Renal Blood Flow during Acute Reduction of Cardiac Output in the Dog

Oliver¹,

Sciacca²,

Pinto³

et al. 1981

J. Clin. Invest.

114

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A B S T R A C T To determine whether renal prostaglandins participate in the regulation of renal blood flow during acute reduction of cardiac output, cardiac venous return was decreased in 17 anesthetized dogs by inflating a balloon placed in the thoracic inferior vena cava. This maneuver decreased cardiac output from 3.69±0.09 liters/min (mean±SEM) to 2. 15±0.19 liters/min (P < 0.01) and the mean arterial blood pressure from 132±4 to 111±5 mm Hg (P < 0.01) and increased total peripheral vascular resistance from 37.6±2.5 to 57.9±4.8 arbitrary resistance units (RU) (P < 0.01). In marked contrast, only slight and insignificant decreases in the renal blood flow from 224±16 to 203± 19 ml/min and renal vascular resistance from 0.66 ±0.06 to 0.61±0.05 arbitrary resistance units (ru) were observed during inflation of the balloon. Concomitant with these hemodynamic changes, plasma renin activity and plasma norepinephrine concentration increased significantly in both the arterial and renal venous bloods. Plasma concentration of prostaglandin E2 in renal venous blood increased from 34±6 to 129±24 pg/ml (P < 0.01). The subsequent administration of indomethacin or meclofenamate had no significant effect on mean arterial pressure, cardiac output, and total peripheral vascular resistance, but reduced renal blood flow from 203±19 to 156±21 ml/min (P < 0.01) and increased renal vascular resistance from 0.61±0.05 to 1.05±0.21 ru (P < 0.01). Simultaneously, the plasma concentration ofprostaglandin E2 in renal venous blood fell from 129±24 to 19±3 pg/ml (P < 0.01). Administration of indomethacin to five dogs without prior obstruction of the inferior vena cava had no effect upon renal blood flow or renal vascular resistance. The results indicate that acute reduction of cardiac output enhances renal renin secretion and the activity of the

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“…The biosynthesis and regulation of prostaglandin-like compounds by catecholamines has been of interest for several years (Levine and Moskowitz, 1979). The ability of the D 2 receptor to mediate the release and metabolism of AA from the intercellular membrane is known (Piomelli et al, 1991;Felder et al, 1991), and although the exact mechanism is not well understood, there has been much discussion as to how it might be regulated by other signaling effectors, most notably AC, MAPK, and PKC (see Chakraborti, 2003 for a review).…”

Section: Discussionmentioning

confidence: 99%

Aripiprazole has Functionally Selective Actions at Dopamine D2 Receptor-Mediated Signaling Pathways

Urban

Vargas

Zastrow

et al. 2006

Neuropsychopharmacol

179

173

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Aripiprazole is a unique atypical antipsychotic drug with an excellent side-effect profile presumed, in part, to be due to lack of typical D 2 dopamine receptor antagonist properties. Whether aripiprazole is a typical D 2 partial agonist, or a functionally selective D 2 ligand, remains controversial (eg D 2 -mediated inhibition of adenylate cyclase is system dependent; aripiprazole antagonizes D 2 receptormediated G-protein-coupled inwardly rectifying potassium channels and guanosine triphosphate nucleotide (GTP)gS coupling). The current study examined the D 2L receptor binding properties of aripiprazole, as well as the effects of the drug on three downstream D 2 receptor-mediated functional effectors: mitogen-activated protein kinase (MAPK) phosphorylation, potentiation of arachidonic acid (AA) release, and D 2 receptor internalization. Unlike quinpirole (a full D 2 agonist) or (À)3PPP (S(À)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride, a D 2 partial agonist), the apparent D 2 affinity of aripiprazole was not decreased significantly by GTP. Moreover, full or partial agonists are expected to have Hill slopes o1.0, yet that of aripiprazole was significantly 41.0. Whereas aripiprazole partially activated both the MAPK and AA pathways, its potency vs MAPK phosphorylation was much lower relative to potencies in assays either of AA release or inhibition of cyclic adenosine 3 0 ,5 0 -cyclic monophosphate accumulation. In addition, unlike typical agonists, neither aripiprazole nor (À)3PPP produced significant internalization of the D 2L receptor. These data are clear evidence that aripiprazole affects D 2L -mediated signaling pathways in a differential manner. The results are consistent with the hypothesis that aripiprazole is a functionally selective D 2 ligand rather than a simple partial agonist. Such data may be useful in understanding the novel clinical actions of this drug.

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α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture

Cited by 61 publications

References 21 publications

Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog.

Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog.

Participation of the Prostaglandins in the Control of Renal Blood Flow during Acute Reduction of Cardiac Output in the Dog

Aripiprazole has Functionally Selective Actions at Dopamine D2 Receptor-Mediated Signaling Pathways

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