PMID- 3676593 OWN - NLM STAT- MEDLINE DCOM- 19871224 LR - 20190510 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 92 IP - 2 DP - 1987 Oct TI - Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. PG - 257-64 AB - 1 The mechanisms by which agents modulate the induction of kinin B1-receptors were investigated by studying the effects of kinins in vitro, by use of the rabbit isolated aorta, and in vivo by measuring the blood pressure of anaesthetized rabbits. 2 The contractile response of the rabbit isolated aorta to kinins increased in a time-dependent manner in vitro. This effect was abolished by continuous exposure to the protein synthesis inhibitor cycloheximide (71 microM). 3 Several substances were found to increase specifically the rate of sensitization to des-Arg9-bradykinin (des-Arg9-Bk), when applied continuously in vitro to tissues isolated from normal animals: bacterial lipopolysaccharide (LPS; 1 micrograms ml-1), muramyl-dipeptide (MDP; 2 micrograms ml-1), phorbol myristate acetate (PMA; 320 nM), epidermal growth factor (EGF; 100 ng ml-1) and endothelial cell growth factor (150 micrograms ml-1). 4 The protease inhibitors phenylmethylsulphonyl fluoride and aprotinin, a non-adjuvant isomer of MDP, rabbit purified leukocyte interferon, fibroblast growth factor and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) did not have this effect. 5. It has been demonstrated that LPS induces B1-receptors in rabbits enabling des-Arg9-Bk to act as a hypotensive agent. In these experiments neutropenia induced by nitrogen mustard, did not prevent the in vivo effect of LPS. MDP (300 micrograms) and PMA (100 micrograms) were also found to induce a state of responsiveness to des-Arg9-Bk in vivo. FMLP (1 mg i.v.) induced a temporary decrease in blood neutrophil counts but had no effect on the induction of responses to des-Arg9-Bk. 6. The development of responses mediated by the B,-receptor in the two experimental systems seems to be unrelated to the activation of neutrophil leukocytes, but may be related to the activation of tissue macrophages. Approximately 3% of cultured adherent cells derived from rabbit aorta strips following protease digestion were stained for non-specific esterase, supporting such a possibility. FAU - Bouthillier, J AU - Bouthillier J AD - Unite de Recherche Inflammation et Immuno-Rhumatologie, Centre Hospitalier de l'Universite Laval, Quebec, Canada. FAU - Deblois, D AU - Deblois D FAU - Marceau, F AU - Marceau F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Kinins) RN - 15958-92-6 (bradykinin, des-Arg(9)-) RN - S8TIM42R2W (Bradykinin) SB - IM MH - Anesthesia MH - Animals MH - Aorta, Thoracic/drug effects MH - Blood Cell Count MH - Blood Pressure/drug effects MH - Bradykinin/*analogs & derivatives/pharmacology MH - Female MH - In Vitro Techniques MH - Kinins/pharmacology MH - Male MH - Muscle Contraction/drug effects MH - Muscle, Smooth, Vascular/drug effects MH - Rabbits PMC - PMC1853641 EDAT- 1987/10/01 00:00 MHDA- 1987/10/01 00:01 PMCR- 1988/10/01 CRDT- 1987/10/01 00:00 PHST- 1987/10/01 00:00 [pubmed] PHST- 1987/10/01 00:01 [medline] PHST- 1987/10/01 00:00 [entrez] PHST- 1988/10/01 00:00 [pmc-release] AID - 10.1111/j.1476-5381.1987.tb11319.x [doi] PST - ppublish SO - Br J Pharmacol. 1987 Oct;92(2):257-64. doi: 10.1111/j.1476-5381.1987.tb11319.x.