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Title: Angiotensin II tachyphylaxis in the guinea pig ileum and its prevention: A pharmacological and biochemical study
Authors: Kanashiro, C. A.
Paiva, T. B.
Paiva, ACM
Prioste, R. N.
Aboulafia, J.
Shimuta, S. I.
Universidade Federal de São Paulo (UNIFESP)
Issue Date: 1-Dec-1995
Publisher: Williams & Wilkins
Citation: Journal Of Pharmacology And Experimental Therapeutics. Baltimore: Williams & Wilkins, v. 275, n. 3, p. 1543-1550, 1995.
Abstract: Angiotensin II (All) tachyphylaxis occurs in the guinea pig ileum, but is not induced by analogs lacking the N-terminal amino group or the Arg(2) guanidino group. Both All and Lys(2)AII increased cell inositol trisphoshate content in cultured intestinal smooth muscle cells. Protein kinase C inhibition by staurosporine or downregulation by prolonged incubation with phorbol reverted tachyphylaxis of the inositol trisphoshate response, but not that of the Na+ uptake response, indicating that the uncoupling of the phosphoinositide signal system by protein kinase C did not involve all processes distal to receptor activation. Tachyphylaxis of the Na+ uptake response was prevented when receptor internalization was blocked by reduction of the temperature (4 degrees C) or by pretreatment of the cells with phenylarsine oxide. Acid washings, which prevented tachyphylaxis of the Na-24(+) influx response, also prevented tachyphylaxis of the contractile response of the guinea pig ileum to AII. Although these findings suggest that sequestration or internalization of the AII receptor might be involved in AII tachyphylaxis, binding of [I-125]AII and of [I-125]Lys(2)AII to the cells was equally unaffected by repeated administrations of the peptides. The results suggest that conformational change of the AII-receptor complex within the plasma membrane, but not internalization, is the most important factor responsible for tachyphylaxis.
ISSN: 0022-3565
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Appears in Collections:Artigo

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