Biomaterial Database

Mechanism of the vascular angiotensin II/alpha2-adrenoceptor interaction. 2005

Edwin K Jackson, and Liping Gao, and Chongxue Zhu

Center for Clinical Pharmacology, Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15219-3130, USA. edj@pitt.edu

alpha(2)-Adrenoceptors potentiate vascular responses to angiotensin II. The goal of this study was to test the hypothesis that the phospholipase C (PLC)/protein kinase C (PKC)/c-src/phosphatidylinositol 3-kinase (PI3K) pathway contributes to the vascular angiotensin II/alpha(2)-adrenoceptor interaction. In rats in vivo, intrarenal infusions of angiotensin II (10 ng/kg/min) increased renal vascular resistance by 5.8 +/- 0.5 units, and this response was enhanced (p < 0.05) to 9.1 +/- 1.2 units by UK-14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine; 3 microg/kg/min; alpha(2)-adrenoceptor agonist]. Intrarenal infusions of U-73122 [1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]-hexyl]-1H-pyrrole-2,5-dione; 3 microg/min; PLC inhibitor], GF109203X [bisindolylmaleimide I; 10 microg/min; PKC inhibitor], CGP77675 [1-(2-{4-[4-amino-5-(3-methoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]phenyl}ethyl)piperidin-4-ol; 5 microg/min; c-src inhibitor], and wortmannin (1 microg/min; PI3K inhibitor) abolished the angiotensin II/alpha(2)-adrenoceptor interaction. In isolated perfused rat kidneys, angiotensin II (0.3, 1, and 3 nM) increased perfusion pressure (by 15 +/- 8, 39 +/- 4, and 93 +/- 9 mm Hg, respectively), and UK-14,304 (1 microM) potentiated these responses (to 36 +/- 4, 67 +/- 7, and 135 +/- 17 mm Hg, respectively). This angiotensin II/alpha(2)-adrenoceptor interaction was abolished by U-73122 (10 microM), GF109203X (3 microM), CGP77675 (5 microM), and wortmannin (0.2 microM). Preglomerular microvascular smooth muscle cells expressed phospholipase (PLC)-beta(2), PLC-beta(3), c-src, phospho(tyrosine 416)-c-src, and PI3K. In these cells, angiotensin II (0.1 microM) and UK-14,304 (1 microM) per se did not increase phospho-c-src; however, the combination of angiotensin II plus UK-14,304 doubled phospho-c-src, and this interaction was abolished by U-73122 (10 microM) and GF109203X (3 microM). In conclusion, the PLC/PKC/c-src/PI3K pathway may contribute importantly to the interaction between alpha(2)-adrenoceptors and angiotensin II on renal vascular resistance.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D010738	Type C Phospholipases	A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.	Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011505	Protein-Tyrosine Kinases	Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.	Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011810	Quinoxalines		Quinoxaline
D011918	Rats, Inbred SHR	A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.	Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D000068438	Brimonidine Tartrate	A quinoxaline derivative and ADRENERGIC ALHPA-2 RECEPTOR AGONIST that is used to manage INTRAOCULAR PRESSURE associated with OPEN-ANGLE GLAUCOMA and OCULAR HYPERTENSION.	5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline D-tartrate,5-bromo-6-(imidazolidinylideneamino)quinoxaline,5-bromo-6-(imidazolin-2-ylamino)quinoxaline,AGN 190342,AGN-190342,Alphagan,Alphagan P,Brimonidine,Brimonidine Purite,Brimonidine Tartrate (1:1),Brimonidine Tartrate (1:1), (S-(R,R))-Isomer,Brimonidine Tartrate, (R-(R,R))-Isomer,Bromoxidine,Mirvaso,Ratio-Brimonidine,Sanrosa,UK 14,304,UK 14,304-18,UK 14304,UK 14308,UK-14,304-18,UK-14,308,UK-14304,AGN190342,Ratio Brimonidine,UK 14,304 18,UK 14,30418,UK 14,308,UK14,30418,UK14,308,UK14304
D000081247	CSK Tyrosine-Protein Kinase	Protein tyrosine kinases that phosphorylate tyrosine residues located in the C-terminal tails of SRC-FAMILY KINASES.	C-Terminal Src Kinase,Carboxy-Terminal Src Kinase,Protein Tyrosine Kinase p50(csk),Protein-Tyrosine Kinase C-Terminal Src Kinase,Protein-Tyrosine Kinase c-src,Tyrosine Protein Kinase p50csk,Tyrosine-Protein Kinase CSK,c-src Kinase,c-src Tyrosine Kinase,CSK-src,p50(csk),C Terminal Src Kinase,CSK Tyrosine Protein Kinase,CSK src,CSK, Tyrosine-Protein Kinase,Carboxy Terminal Src Kinase,Kinase CSK, Tyrosine-Protein,Kinase c-src, Protein-Tyrosine,Kinase, C-Terminal Src,Kinase, CSK Tyrosine-Protein,Kinase, Carboxy-Terminal Src,Kinase, c-src,Kinase, c-src Tyrosine,Protein Tyrosine Kinase C Terminal Src Kinase,Protein Tyrosine Kinase c src,Src Kinase, C-Terminal,Src Kinase, Carboxy-Terminal,Tyrosine Kinase, c-src,Tyrosine Protein Kinase CSK,Tyrosine-Protein Kinase, CSK,c src Kinase,c src Tyrosine Kinase,c-src, Protein-Tyrosine Kinase