TY - JOUR
T1 - Two dissimilar AT1 agonists distinctively activate AT1 receptors located on the luminal membrane of coronary endothelium
AU - Castillo-Hernández, Jesús
AU - Torres-Tirado, David
AU - Barajas-Espinosa, Alma
AU - Chi-Ahumada, Erika
AU - Ramiro-Díaz, Juan
AU - Ceballos, Guillermo
AU - Rubio, Rafael
N1 - Funding Information:
Supported by: Research Grants CONACYT # SEP - 2003 - CO2 - 42567 A - 1 and # SSS - 2004 - COI - 156 , UASLP # CO7-FRC-02-23.41, Fellowships and Research Supports CONACYT #183141, #158223, #182615, and #218980. Thanks to AR Barajas, JR Castillo, JM Ramiro and D. Torres.
PY - 2009/11
Y1 - 2009/11
N2 - Diverse intracoronary agonists cause cardiac effects while acting on coronary endothelial luminal membrane (CELM) receptor. Our data show: a) the presence of AT1R in isolated CELM and in all cardiac cell types and b) sustained intracoronary infusions of Ang II-POL, a large sized molecule (~ 15,000 kDa) confined to the vessel lumen that can only act on CELM's AT1R or Ang II (~ 1 kDa); both exert the same maximum positive inotropic (PIE) and coronary constriction (CPP). The effects of these two agonists are blocked by Losartan and by Sar-POL; a large size antagonist (~ 15,000 kDa) that acts only on CELM. Ang II effects are transient due to desensitization and cause tachyphylaxis to Ang II and toward Ang II-POL suggesting that both Ang II and Ang II-POL act on the same receptor group. In contrast, Ang II-POL effects are sustained and do not cause tachyphylaxis. The results show that intravascular Ang II and Ang II-POL act differentially by an unknown mechanism on CELM's AT1R and suggest that intravascular Ang II and Ang II-POL cause PIE and CCP by activation limited to CELM's AT1R through an unknown mechanism that is space-confined to the CELM's AT1R.
AB - Diverse intracoronary agonists cause cardiac effects while acting on coronary endothelial luminal membrane (CELM) receptor. Our data show: a) the presence of AT1R in isolated CELM and in all cardiac cell types and b) sustained intracoronary infusions of Ang II-POL, a large sized molecule (~ 15,000 kDa) confined to the vessel lumen that can only act on CELM's AT1R or Ang II (~ 1 kDa); both exert the same maximum positive inotropic (PIE) and coronary constriction (CPP). The effects of these two agonists are blocked by Losartan and by Sar-POL; a large size antagonist (~ 15,000 kDa) that acts only on CELM. Ang II effects are transient due to desensitization and cause tachyphylaxis to Ang II and toward Ang II-POL suggesting that both Ang II and Ang II-POL act on the same receptor group. In contrast, Ang II-POL effects are sustained and do not cause tachyphylaxis. The results show that intravascular Ang II and Ang II-POL act differentially by an unknown mechanism on CELM's AT1R and suggest that intravascular Ang II and Ang II-POL cause PIE and CCP by activation limited to CELM's AT1R through an unknown mechanism that is space-confined to the CELM's AT1R.
KW - ATR activation without desensitization
KW - Compartmentalization of hormone action
KW - Desensitization
KW - Endothelial luminal AT receptors
KW - Tachyphylaxis
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U2 - 10.1016/j.vph.2009.07.003
DO - 10.1016/j.vph.2009.07.003
M3 - Article
C2 - 19643203
AN - SCOPUS:70449109326
SN - 1537-1891
VL - 51
SP - 314
EP - 322
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 5-6
ER -