title: Self suppression of phosphoinositide turnover and contraction by stimulating release of endogenous endothelium derived relaxing factor in vascular action of histamine.
abstract: OBJECTIVE
  The aim of the study was to examine the relationship between phosphoinositide turnover and vascular contraction in response to histamine, and the role of endothelium derived relaxing factor (EDRF) in these activities.
  
  
  METHODS
  Thoracic aortic strips were studied under isometric tension in an organ bath. Phosphoinositide turnover was studied using [32P]Pi labelling. Cumulative concentration-response curves were obtained for histamine, and for histamine plus H1 and H2 antagonists. The effect of endothelial denudation was examined, as was that of removing Ca2+ from buffer medium, and of adding methylene blue, an inhibitor of EDRF. EXPERIMENTAL PREPARATIONS: Thoracic aortic rings were obtained from 81 male Japanese white rabbits, weight 2.0-2.4 kg.
  
  
  RESULTS
  Histamine (0.1 mumol-0.1 mmol.litre-1) caused concentration dependent contractions and increases of [32P]Pi incorporation into phosphatidylinositol (ED50 = 4.6 mumol.litre-1 and 4.0 mumol.litre-1 respectively). Diphenhydramine inhibited contractile response and phosphatidylinositol labelling by histamine. Cimetidine potentiated contractile response but had no effect on phosphatidylinositol labelling. Endothelial denudation potentiated maximum contraction by 15% and augmented phosphatidylinositol labelling at 0.1 mmol.litre-1 histamine by 30%. In intact aortic rings, methylene blue (10 mumol.litre-1), an inhibitor of EDRF, potentiated histamine induced phosphatidylinositol labelling, but had no influence on denuded rings. A-23187 (0.01 mumol.litre-1), which caused release of EDRF from intact endothelium, suppressed histamine induced phosphatidylinositol labelling in intact aortic rings.
  
  
  CONCLUSIONS
  The results suggest that stimulation of the release of EDRF in response to histamine causes self suppression of phosphoinositide turnover and contraction.
authors.affiliation: First Department of Internal Medicine, Kobe University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishimoto
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Fukuzaki
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011817:Rabbits
chemical_list: D010716:Phosphatidylinositols; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D000001:Calcimycin; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D006152:Cyclic GMP; D002118:Calcium; D008751:Methylene Blue