Angiotensin II tachyphylaxis in the guinea pig ileum and its prevention: a pharmacological and biochemical study.
Angiotensin II (AII) tachyphylaxis occurs in the guinea pig ileum, but is not induced by analogs lacking the N-terminal amino group or the Arg2 guanidino group. Both AII and Lys2AII 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 24Na+ 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 [125I]AII and of [125I]Lys2AII 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.
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
C A
CA
Kanashiro
T B
TB
Paiva
A C
AC
Paiva
R N
RN
Prioste
J
J
Aboulafia
S I
SI
Shimuta
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003080:Cold Temperature; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism; D019311:Staurosporine; D013618:Tachyphylaxis
D000470:Alkaloids; D001152:Arsenicals; C029341:oxophenylarsine; D000804:Angiotensin II; C058393:angiotensin II, Lys(2)-; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium