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PMID:15598876
| Citation |
Yang, Z, Asico, LD, Yu, P, Wang, Z, Jones, JE, Bai, RK, Sibley, DR, Felder, RA and Jose, PA (2005) D5 dopamine receptor regulation of phospholipase D. Am. J. Physiol. Heart Circ. Physiol. 288:H55-61 |
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| Abstract |
D(1)-like receptors have been reported to decrease oxidative stress in vascular smooth muscle cells by decreasing phospholipase D (PLD) activity. However, the PLD isoform regulated by D(1)-like receptors (D(1) or D(5)) and whether abnormal regulation of PLD by D(1)-like receptors plays a role in the pathogenesis of hypertension are unknown. The hypothesis that the D(5) receptor is the D(1)-like receptor that inhibits PLD activity and serves to regulate blood pressure was tested using D(5) receptor mutant mice (D(5)(-/-)). We found that in the mouse kidney, PLD2, like the D(5) receptor, is mainly expressed in renal brush-border membranes, whereas PLD1 is mainly expressed in renal vessels with faint staining in brush-border membranes and collecting ducts. Total renal PLD activity is increased in D(5)(-/-) mice relative to congenic D(5) wild-type (D(5)(+/+)) mice. PLD2, but not PLD1, expression is greater in D(5)(-/-) than in D(5)(+/+) mice. The D(5) receptor agonist fenoldopam decreases PLD2, but not PLD1, expression and activity in human embryonic kidney-293 cells heterologously expressing the human D(5) receptor, effects that are blocked by the D(5) receptor antagonist SCH-23390. These studies show that the D(5) receptor regulates PLD2 activity and expression. The hypertension in the D(5)(-/-) mice is associated with increased PLD expression and activity. Impaired D(5) receptor regulation of PLD2 may play a role in the pathogenesis of hypertension. |
| Links |
PubMed Online version:10.1152/ajpheart.00627.2004 |
| Keywords |
Animals; Blood Pressure/physiology; CHO Cells; Cell Line; Cricetinae; Cricetulus; Humans; Kidney/enzymology; Mice; Mice, Knockout; Phospholipase D/genetics; Phospholipase D/metabolism; RNA, Messenger/metabolism; Receptors, Dopamine D1/metabolism; Receptors, Dopamine D1/physiology; Receptors, Dopamine D5; Tissue Distribution |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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