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Human vascular kinin receptors of the B2 type characterized by radioligand binding.
Br J Pharmacol. 1997 Dec; 122(7):1450-4.BJ

Abstract

1. The human umbilical vein responds to bradykinin (BK) with contractions that are mediated by B2 receptors. In the present study, the corresponding vascular smooth muscle B2 binding sites have been investigated. 2. [3H]-BK, a full agonist labelled ligand, was used to demonstrate a single binding site giving a Kd value of 0.51+/-0.02 nM and a Bmax of 24+/-1 fmol mg(-1) protein. Scatchard plots were linear (r=0.98) in the 0.05-5 nM range of concentrations. Non-specific binding was found to be 30% of total binding. 3. Competition binding curves gave the following order of potency for various B2 receptor agonists: BK-[Hyp3]-BK > or = Lys-BK >> [Aib7]-BK >>> [desArg9]-BK, which is typical of B2 receptors. There was no binding to B1 receptors since the selective B1 receptor ligand, Lys-[desArg9]BK was inactive up to 10 microM (n=4). 4. Characterization of the binding site with antagonists, performed with three chemically distinct series of peptide and non-peptide compounds, revealed a high affinity of Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK) (Ki 0.17 nM; n=4) which was more potent that FR 173657 ([(E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinol inyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide]) (Ki 1.94 nM; n=4), D-Arg-[Hyp3,D-Phe7,Leu8]-BK (Ki 256 nM; n=4) and Win 64338 (phosphonium, [[4[[2[[bis(cyclohexylamino)methylene]amino]-3-(2-naphthalenyl)-1-oxopro pyl]amino]phenyl]methyl]tributyl, chloride, monohydrochloride) (Ki 1,450 nM; n=4). 5. The present study describes and characterises B2 receptor binding sites in the vascular smooth muscle of the human umbilical vein. The binding assay appears to be suitable for studying new agonists or antagonists designed to activate or block the B2 receptor class that mediate the majority of the physiopathological effects of kinins in man.

Authors+Show Affiliations

Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9421294

Citation

Gessi, S, et al. "Human Vascular Kinin Receptors of the B2 Type Characterized By Radioligand Binding." British Journal of Pharmacology, vol. 122, no. 7, 1997, pp. 1450-4.
Gessi S, Rizzi A, Calò G, et al. Human vascular kinin receptors of the B2 type characterized by radioligand binding. Br J Pharmacol. 1997;122(7):1450-4.
Gessi, S., Rizzi, A., Calò, G., Agnello, G., Jorizzo, G., Mollica, G., Borea, P. A., & Regoli, D. (1997). Human vascular kinin receptors of the B2 type characterized by radioligand binding. British Journal of Pharmacology, 122(7), 1450-4.
Gessi S, et al. Human Vascular Kinin Receptors of the B2 Type Characterized By Radioligand Binding. Br J Pharmacol. 1997;122(7):1450-4. PubMed PMID: 9421294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human vascular kinin receptors of the B2 type characterized by radioligand binding. AU - Gessi,S, AU - Rizzi,A, AU - Calò,G, AU - Agnello,G, AU - Jorizzo,G, AU - Mollica,G, AU - Borea,P A, AU - Regoli,D, PY - 1998/1/8/pubmed PY - 1998/1/8/medline PY - 1998/1/8/entrez SP - 1450 EP - 4 JF - British journal of pharmacology JO - Br J Pharmacol VL - 122 IS - 7 N2 - 1. The human umbilical vein responds to bradykinin (BK) with contractions that are mediated by B2 receptors. In the present study, the corresponding vascular smooth muscle B2 binding sites have been investigated. 2. [3H]-BK, a full agonist labelled ligand, was used to demonstrate a single binding site giving a Kd value of 0.51+/-0.02 nM and a Bmax of 24+/-1 fmol mg(-1) protein. Scatchard plots were linear (r=0.98) in the 0.05-5 nM range of concentrations. Non-specific binding was found to be 30% of total binding. 3. Competition binding curves gave the following order of potency for various B2 receptor agonists: BK-[Hyp3]-BK > or = Lys-BK >> [Aib7]-BK >>> [desArg9]-BK, which is typical of B2 receptors. There was no binding to B1 receptors since the selective B1 receptor ligand, Lys-[desArg9]BK was inactive up to 10 microM (n=4). 4. Characterization of the binding site with antagonists, performed with three chemically distinct series of peptide and non-peptide compounds, revealed a high affinity of Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK) (Ki 0.17 nM; n=4) which was more potent that FR 173657 ([(E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinol inyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide]) (Ki 1.94 nM; n=4), D-Arg-[Hyp3,D-Phe7,Leu8]-BK (Ki 256 nM; n=4) and Win 64338 (phosphonium, [[4[[2[[bis(cyclohexylamino)methylene]amino]-3-(2-naphthalenyl)-1-oxopro pyl]amino]phenyl]methyl]tributyl, chloride, monohydrochloride) (Ki 1,450 nM; n=4). 5. The present study describes and characterises B2 receptor binding sites in the vascular smooth muscle of the human umbilical vein. The binding assay appears to be suitable for studying new agonists or antagonists designed to activate or block the B2 receptor class that mediate the majority of the physiopathological effects of kinins in man. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9421294/Human_vascular_kinin_receptors_of_the_B2_type_characterized_by_radioligand_binding_ L2 - https://doi.org/10.1038/sj.bjp.0701536 DB - PRIME DP - Unbound Medicine ER -