125I[Sar(1)Ile(8)] angiotensin II has a different affinity for AT(1) and AT(2) receptor subtypes in ovine tissues.
Iodinated angiotensin II (Ang II) and its analogues are often assumed to have equal affinities for AT(1) and AT(2) receptor subtypes. However, using saturation and competition binding assays in several tissues from pregnant, nonpregnant, and fetal sheep, we found the affinity of 125I[Sar(1)Ile(8)] Ang II for Ang II receptors was different (P<0.05) between tissue types. The dissociation constants (Kd) and half maximal displacements of [Sar(1)Ile(8)] Ang II (Sar IC(50)) were directly related (P<0.05) to proportions of AT(1) receptors, and inversely related (P<0.05) to proportions of AT(2) receptors in tissues from all groups combined, in tissues from individual groups (pregnant, nonpregnant or fetal), and in some individual tissues (uterine arteries and aortae). This suggests that 125I[Sar(1)Ile(8)] Ang II has a different affinity for AT(1) and AT(2) receptors in ovine tissues. The Kds of 125I[Sar(1)Ile(8)] Ang II for "pure" populations of AT(1) and AT(2) receptors were 1.2 and 0.3 nM, respectively, i.e. affinity was four-fold higher for AT(2) receptors. We corrected the measured proportions of the receptor subtypes using their fractional occupancies. In tissues which contained at least 10% of each receptor subtype, the corrected proportions were significantly altered (P<0.05), even in some tissues, to the extent of being reversed.
McMullen
Julie R
JR
School of Physiology and Pharmacology, University of New South Wales, 2052, Sydney, Australia.
Gibson
Karen J
KJ
Lumbers
Eugenie R
ER
Burrell
Judith H
JH
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism; D000809:Angiotensins / Q000819:agonists / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D019808:Losartan / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012756:Sheep; D014599:Uterus / Q000098:blood supply
D000809:Angiotensins; D007093:Imidazoles; D007457:Iodine Radioisotopes; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C073402:PD 123319; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D019808:Losartan