Receptor binding interactions of the angiotensin II antagonist, 125I-[sarcosine1,leucine8]angiotensin II, with mammalian brain and peripheral tissues.
Sarcosine1,leucine8-angiotensin II ([Sar1,Leu8]AII), an angiotensin II antagonist, binds saturably, reversibly and with high affinity (KD's of 0.03-22 nM) to calf cerebellar cortex, bovine adrenal cortex and rabbit uterine membranes. The peptide specificity of 125I[Sar1,Leu8]AII binding to brain, adrenal cortex and uterus is consistent with the labeling of physiologically relevant angiotensin receptors. A detailed study of the binding potencies of 28 angiotensin peptide analogues reveals: (1) very significant correlations between peptide binding potencies at 125I-AII compared to 125I-[Sar1,Leu8]AII binding sites, (2) many similarities between brain and uterine receptor sites and marked differences between these two tissue receptors compared to adrenal cortical receptor sites, and (3) correlations among peptide physiological potencies (AII-contracted rabbit aortic strip) and receptor binding potencies in all three tissues labeled with either 125I-AII or 125I-[Sar1,Leu8]AII. The correlations are much better for adrenal cortex than for brain or uterus, suggesting that adrenal cortical angiotensin receptors are similar to aorta angiotensin receptors.
D000302:Adrenal Cortex / Q000187:drug effects; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002417:Cattle; D004798:Enzymes / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009928:Organ Specificity; D011817:Rabbits; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D004798:Enzymes; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; C009210:sarleucin