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Angiotensin II [Sar1. Gly8], A Selective Antagonist for Angiotensin II Receptor AT(1)
Sarcosine(1),glycine(8) angiotensin II is an AT(1) angiotensin II receptor subtype selective antagonist
Studies predating the discovery of the two major subtypes of angiotensin
II (Ang II) receptors, AT(1) and AT(2), revealed anomalous characteristics
of sarcosine(1),glycine(8) Ang II (Sar(1),Gly(8) Ang II). It competed
poorly for 125I-Ang II binding in bovine brain but potently antagonized
dipsogenic responses to intracerebroventricularly administered Ang II.
Subsequent recognition that bovine brain contains AT(2) receptors, while
dipsogenic responses to Ang II are mediated by AT(1) receptors, suggests
that Sar(1),Gly(8) Ang II is AT(1) selective. Sar(1),Gly(8) Ang II competed
for 125I-sarcosine(1),isoleucine(8) Ang II binding to AT(1) receptors
in pituitary, liver and adrenal (the latter with the AT(2) selective antagonist
PD 123,319) with K(i)'s of 0.66, 1.40 and 1.36 nM, respectively. In contrast,
the K(i) of Sar(1),Gly(8) Ang II for AT(2) receptors in rat adrenal (with
the selective AT(1) antagonist losartan) was 52 nM. 125I-Sar(1),Gly(8)
Ang II (0.5-3 nM) bound to AT(1) receptors in pituitary, liver, heart,
adrenal, and hypothalamic membranes with high affinity (K(d)=0.43, 1.6,
2.3, 0.96 and 1.8 nM, respectively), but showed no saturable binding to
the adrenal AT(2) receptor. 125I-Sar(1),Gly(8) Ang II selectively labeled
AT(1) receptors in sections of adrenal using receptor autoradiography.
Thus, binding studies reveal Sar(1),Gly(8) Ang II to be the first angiotensin
peptide analog to show AT(1) receptor selectivity. 125I-Sar(1),Gly(8)
Ang II offers a new means to selectively radiolabel AT(1) receptors and
may help to characterize ligand docking sites and agonist switches for
AT(1) versus AT(2) receptors.
Speth RC. Regul Pept. 2003 Oct 15;115(3):203-9
Stimulation of collagen gel contraction by angiotensin II and III in
cardiac fibroblasts
OBJECTIVE: The aim of the present study was to investigate whether angiotensin
II (Ang II), angiotensin III (Ang III) or Ang II (2-8), angiotensin IV
(Ang IV) or Ang II (3-8) and Ang II (1-7), Ang II (4-8), Ang II (5-8)
and Ang II (1-4) can stimulate collagen gel contraction in cardiac fibroblasts
in serum-free conditions. METHODS: Cardiac fibroblasts (from male adult
Wistar rats) from passage 2 were cultured to confluency and added to a
hydrated collagen gel in a Dulbecco's Modified Eagle's Medium, with or
without foetal bovine serum, for one, two or three days. The area of the
collagen gels embedded with cardiac fibroblasts was determined by a densitometric
analysis. Collagen gel contraction was characterised by a decrease in
the gel area. RESULTS: Ang II dose-dependently stimulated the contraction
of collagen mediated by cardiac fibroblasts after one, two or three days
of incubation in a serum-free medium. Telmisartan completely blocked the
Ang II-induced collagen contraction by cardiac fibroblasts. PD 123319
and des-Asp(1)-Ile(8)-Ang II had no effect on the Ang II-induced collagen
contraction by cardiac fibroblasts. Ang III also stimulated the contraction
of collagen mediated by cardiac fibroblasts after one, two or three days
of incubation in a serum-free medium. des-Asp(1)-Ile(8)-Ang II and telmisartan
completely blocked the Ang III-induced collagen gel contraction by cardiac
fibroblasts. des-Asp(1)-Ile(8)-Ang II, however, had no effect on the Ang
II-induced collagen gel contraction by cardiac fibroblasts. Ang IV and
Ang II (4-8), (5-8), (1-7) and (1-4), however, had no effect on collagen
gel contraction by cardiac fibroblasts. Addition of telmisartan, PD 123319
or des-Asp(1)-Ile(8)-Ang II alone did not affect collagen gel contraction
by cardiac fibroblasts. CONCLUSION: Our data demonstrate that the effects
of Ang II on the collagen gel contraction by adult rat cardiac fibroblasts
in serum-free conditions are Ang II type 1(AT(1))-receptor- mediated,
because they are abolished by the specific AT(1)-receptor antagonist,
telmisartan, and not by the AT(2)-receptor antagonist PD 123319 or by
the Ang III antagonist des-Asp(1)-Ile(8)-angiotensin. The Ang III- stimulated
contraction of collagen by cardiac fibroblasts is completely blocked by
the Ang III receptor antagonist, des-Asp(1)-Ile(8)-angiotensin II, and
by telmisartan.
Lijnen P, et al. J Renin Angiotensin Aldosterone Syst 2002 Sep;3(3):160-6
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Angiotensin Related Products |
| Product Name | Sequence | Catalog No. | Price: USD/Euro |
| Angiotensin II [Sar1 Gly8] | Sar-Arg-Val-Tyr-Ile-His-Pro-Gly | 002-20 | 40.00/5 mg |
| Angiotensin II [Sar1 Gly8], 125I labeled | T-002-20 | 450.00/10uCi | |
| Angiotensin II [Sar1 Gly8], Biotin labeled | B-002-20 | 200.00/20ug | |
| Angiotensin II [Sar1 Gly8], FAM labeled | FG-002-20 | 200.00/1nmole | |
| Angiotensin II [Sar1 Gly8], Rhodamine labeled | FR-002-20 | 200.00/1nmole | |
| Angiotensin II [Sar1 Ile8] | Sar-Arg-Val-Tyr-Ile-His-Pro-Ile | 002-21 | 40.00/5 mg |
| Angiotensin II [Sar1 Ile8], Biotin labeled | B-002-21 | 200.00/20ug | |
| Angiotensin II [Sar1 Ile8], FAM labeled | FG-002-21 | 200.00/1nmole | |
| Angiotensin II [Sar1 Ile8], Rhodamine labeled | FR-002-21 | 200.00/1nmole |
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| Speth R. C. et al. Regulatory Peptides 115(2003) 203-209 |
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Speth R. C. et al. Regulatory Peptides 115(2003) 203-209 |
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| Speth R. C. et al. Regulatory Peptides 115(2003) 203-209 |
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Speth R. C. et al. Regulatory Peptides 115(2003) 203-209 |
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