Further analysis of the upregulation of bradykinin B1 receptors in isolated rabbit aorta by using metabolic inhibitors.
Kinins exert a contractile effect that develops as a function of the in vitro incubation time with isolated rabbit aorta. This response is mediated via receptors of the bradykinin B1 type and interleukin-1 amplifies this upregulation process. Tissues continuously treated with the protein synthesis inhibitor cycloheximide (71 microM) or with the protein trafficking inhibitor, brefeldin A (18 microM), failed to develop a contractile response to the bradykinin B1 receptor agonist, des-Arg9-bradykinin (1.7 microM) (72-100% inhibition of kinin response recorded at 3 or 6 h), whether or not they were exposed to interleukin-1 beta (290 pM). The protein glycosylation inhibitor tunicamycin exerted a selective and significant, but partial (50-76%), inhibition of des-Arg9-bradykinin-induced responses. The biochemical effect of the metabolic inhibitors on the tissue has been validated in assays involving incorporation of [3H]leucine and of [3H]mannose into protein or glycoprotein fractions, respectively. The modulatory effects of metabolic inhibitors on the responses to kinins of the isolated rabbit aorta support the idea that a de novo formation of membrane bradykinin B1 receptors is the molecular basis of both the spontaneous and the interleukin-1-stimulated upregulation phenomenon.
Audet
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R
Centre de Recherche de l'Hôtel-Dieu de Québec, Canada.
Petitclerc
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E
Drapeau
G
G
Rioux
F
F
Marceau
F
F
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D020126:Brefeldin A; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D010649:Phenylalanine / Q000494:pharmacology; D011817:Rabbits; D018002:Receptors, Bradykinin / Q000096:biosynthesis*; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects
D003517:Cyclopentanes; D007375:Interleukin-1; D018002:Receptors, Bradykinin; D014415:Tunicamycin; C024626:bradykinin, des-Arg(9)-; D020126:Brefeldin A; D010649:Phenylalanine; D003513:Cycloheximide; D001920:Bradykinin