title: Angiotensin II and angiotensin-(1-7) inhibit the inner cortex Na+ -ATPase activity through AT2 receptor.
abstract: In the present paper, the modulation of the basolateral membrane (BLM) Na+ -ATPase activity of inner cortex from pig kidney by angiotensin II (Ang II) and angiotensin-(1-7) (Ang-(1-7)) was evaluated. Ang II and Ang-(1-7) inhibit the Na+ -ATPase activity in a dose-dependent manner (from 10(-11) to 10(-5) M), with maximal effect obtained at 10(-7) M for both peptides. Pharmacological evidences demonstrate that the inhibitory effects of Ang II and Ang-(1-7) are mediated by AT2 receptor: The effect of both polypeptides is completely reversed by 10(-8) M PD 123319, a selective AT2 receptor antagonist, but is not affected by either (10(-12) - 10(-5) M) losartan or (10(-10)-10(-7) M) A779, selective antagonists for AT1 and AT(1-7) receptors, respectively. The following results suggest that a PTX-insensitive, cholera toxin (CTX)-sensitive G protein/adenosine 3',5'-cyclic monophosphate (cAMP)/PKA pathway is involved in this process: (1) the inhibitory effect of both peptides is completely reversed by 10(-9) M guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS; an inhibitor of the G protein activity), and mimicked by 10(-10) M guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS; an activator of the G protein activity); (2) the effects of both peptides are mimicked by CTX but are not affected by PTX; (3) Western blot analysis reveals the presence of the Gs protein in the isolated basolateral membrane fraction; (4) (10(-10)-10(-6) M) cAMP has a similar and non-additive effect to Ang II and Ang-(1-7); (5) PKA inhibitory peptide abolishes the effects of Ang II and Ang-(1-7); and (6) both angiotensins stimulate PKA activity.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-Bloco G, 21949-900, RJ, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: De Souza
authors.forename: A G
authors.initials: AG
authors.lastname: Lopes
authors.forename: C P
authors.initials: CP
authors.lastname: Pizzino
authors.forename: R N
authors.initials: RN
authors.lastname: Fossari
authors.forename: N C O
authors.initials: NC
authors.lastname: Miguel
authors.forename: F P
authors.initials: FP
authors.lastname: Cardozo
authors.forename: R
authors.initials: R
authors.lastname: Abi-Abib
authors.forename: M S
authors.initials: MS
authors.lastname: Fernandes
authors.forename: D P A
authors.initials: DP
authors.lastname: Santos
authors.forename: C
authors.initials: C
authors.lastname: Caruso-Neves
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: C092006:7-Ala-angiotensin (1-7); D000276:Adjuvants, Immunologic; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D000803:Angiotensin I; D000242:Cyclic AMP; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase; C118790:angiotensin I (1-7); D019808:Losartan