Up-regulation of [3H]-des-Arg10-kallidin binding to the bradykinin B1 receptor by interleukin-1β in isolated smooth muscle cells: correlation with B1 agonist-induced PGI2 production
| Autor: | B. Chapelain, S. M. Ly, M. C. Bodinier, L. Coussy, T. Jean, Ss. Giraud, J. P. Galizzi, G. Neliat |
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| Rok vydání: | 1994 |
| Předmět: |
Lipopolysaccharides
Agonist medicine.medical_specialty medicine.drug_class Bradykinin In Vitro Techniques Biology Nitric Oxide Muscle Smooth Vascular chemistry.chemical_compound Internal medicine medicine Animals Binding site Receptor IC50 Bradykinin Receptor Antagonists Pharmacology Kallidin Receptors Bradykinin musculoskeletal system Receptor antagonist Epoprostenol Mesenteric Arteries Up-Regulation Dissociation constant Endocrinology chemistry Rabbits Interleukin-1 Signal Transduction Research Article |
| Zdroj: | British Journal of Pharmacology. 113:389-394 |
| ISSN: | 0007-1188 |
| Popis: | 1. Binding of the specific bradykinin B1 receptor agonist, [3H]-des-Arg10-kallidin (-KD) was investigated in smooth muscle cells (SMC) isolated from rabbit mesenteric arteries (RMA). 2. [3H]-des-Arg10-KD specifically bound to interleukin-1 (IL-1)-treated RMA-SMC in a saturable fashion with an equilibrium dissociation constant (KD) of 0.3-0.5 nM. The number of binding sites per cell was 20,000-35,000. Kinins inhibited [3H]-des-Arg10-KD binding to RMA-SMC with an order of potency very similar to that observed in typical B1 specific bioassays: des-Arg9-bradykinin (BK) approximately KDBK. Furthermore, the B1 receptor antagonist [Leu8]des-Arg9-BK inhibited [3H]-des-Arg10-KD binding with an IC50 of 43 nM as expected for its effect at B1 receptors. The B2 receptor antagonists, NPC 567 and Hoe 140 only affected [3H]-des-Arg10-KD binding at very high concentrations (IC50 = 0.8 microM and IC5010 microM, respectively). 3. Des-Arg9-BK (B1 agonist) and [Hyp3]Tyr(Me)8-BK (B2 agonist) did not induce prostacyclin (PGI2) production by RMA-SMC. Lipopolysaccharide (LPS) treatment of the cells did not affect the B1 agonist response whereas IL-1 beta treatment produced a 7 fold increase in des-Arg9-BK-stimulated PGI2 production. IL-1 beta also stimulated the response to B2 agonists. 4. Des-Arg9-BK-induced PGI2 secretion in IL-1-primed RMA-SMC was mediated by B1 receptors since it was inhibited by [Leu8]des-Arg9-BK (IC50 = 56-73 nM) but not by Hoe 140. High concentrations of NPC 567 (IC5o = 2.4 micro M) were required to inhibit PGI2 production induced by B1 agonists.5. IL- 1-treated RMA-SMC displayed a 5 fold increase in the number of B1 receptors without modification of the affinity constant, thus establishing a possible relationship between the receptor density and the IL-i-primed B1 response.6. LPS treatment of the cells induced a 4 fold increase in B1 receptor number without modifying PGI2 secretion. This observation suggests that IL-1 but not LPS, in addition to increase in the number of receptors, signals the cell to permit the coupling of B1 receptors to the PLA2/cyclo-oxygenase pathway. |
| Databáze: | OpenAIRE |
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