Akademik Veri Yönetim Sistemi
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, cilt.273, sa.1, 1997 (SCI-Expanded)
Infusion of norepinephrine (NE) in rats results in desensitization of NE-mediated aortic contraction and a reduction (55% at 1 and 10 mu M) in NE-stimulated vascular inositol phosphate accumulations. The functional responses to angiotensin II (ANG II) were also reduced in the tissues of NE-infused animals. alpha(1)-Adrenoceptor number determined by 2-[beta-(4-hydroxy-3-[I-125]iodophenyl)-ethylaminomethyl]-tetralone ([I-125]HEAT) binding and levels of G alpha or G beta proteins measured by immunoblot analyses were not changed in the aortic membranes of NE-infused animals. To determine whether desensitization is associated with receptor-G protein uncoupling, agonist-stimulated palmitoylation of G alpha proteins was measured. NE infusion decreased phenylephrine (1 mu M)stimulated [H-3]palmitate incorporation into G(q) alpha, G(s) alpha, and G(i) alpha proteins and ANG II (10 mu M)-stimulated palmitoylation of G(q) alpha and G(i) alpha in aortic membranes. Phenylephrine- and ANG II-stimulated guanosine 5'-O-(3-[S-35]thiotriphosphate) binding to G(q) alpha was also decreased in the aortas of NE-infused animals. These results show that an infusion of NE causes heterologous desensitization of the contractile and inositol phosphate accumulation responses in the rat aorta and that these changes are mediated by an uncoupling of receptors from their G proteins.