Modulatory effect of bradykinin on noradrenaline release in isolated atria from normal and B2 knockout transgenic mice
| Autor: | Sylvain Foucart, Chantal Chulak, Réjean Couture |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Bisindolylmaleimide
medicine.medical_specialty Diclofenac Enalaprilat Receptor Bradykinin B2 Bradykinin Mice Transgenic Peptidyl-Dipeptidase A chemistry.chemical_compound Mice Norepinephrine Internal medicine medicine Animals Lysine Carboxypeptidase Cyclooxygenase Inhibitors Bradykinin receptor Receptor Bradykinin Receptor Antagonists Protein Kinase C Pharmacology Mice Knockout biology Myocardium Receptors Bradykinin Heart Electric Stimulation Up-Regulation Endocrinology chemistry Mechanism of action ACE inhibitor biology.protein Prostaglandins Female Cyclooxygenase medicine.symptom medicine.drug |
| Zdroj: | European journal of pharmacology. 346(2-3) |
| ISSN: | 0014-2999 |
| Popis: | The modulatory effect of bradykinin on electrically-induced noradrenaline release was assessed in isolated atria from normal and B2 knockout transgenic mice preincubated with [3H]noradrenaline. Concentrations of 1, 3 and 10 nM of bradykinin did not significantly alter the outflow of radioactivity whereas higher concentrations of bradykinin (30 and 100 nM) enhanced it. The facilitatory effect of 30 nM bradykinin was inhibited by a selective bradykinin B2 receptor antagonist. Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, 30 nM), and by a protein kinase C inhibitor, bisindolylmaleimide (1 microM). The co-administration of bradykinin (1 to 100 nM) with either [Leu8]des-Arg9-bradykinin (100 nM), AcLys[DbetaNal7,Ile8]des-Arg9-bradykinin (30 nM) (bradykinin B1 receptor antagonists) or diclofenac (1 microM) (a cyclooxygenase inhibitor), shifted the facilitatory effect of bradykinin to lower concentrations. The facilitatory effect of bradykinin also was enhanced by enalaprilat (1 microM) and mergetpa (1 microM), inhibitors of angiotensin-converting enzyme (kininase II) and kininase I, respectively. In contrast, selective bradykinin B1 receptor agonists, des-Arg9-bradykinin (1 to 100 nM) and Sar[D-Phe8]des-Arg7-bradykinin (1 to 100 nM), did not significantly affect the stimulation-induced outflow of radioactivity. Neither bradykinin (100 nM) nor des-Arg9-bradykinin (100 nM) had any modulatory effect in B2 knockout transgenic mice. These findings suggest that the facilitatory effect of bradykinin on noradrenaline release in the mouse atria is mediated exclusively by presynaptic bradykinin B2 receptors which are linked to protein kinase C. The greater release of noradrenaline with bradykinin under inhibition of prostaglandins production and kininases I and II activity might be of importance in pharmacotherapies. |
| Databáze: | OpenAIRE |
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