title: Mechanisms underlying lysophosphatidylcholine-induced potentiation of vascular contractions in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat aorta.
abstract: OBJECTIVE
  The effect of lysophosphatidylcholine (LPC) on aortic contractions in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic model, was studied.
  
  
  METHODS
  Using OLETF rats and control (Long Evans Tokushima Otsuka (LETO)) rats, the effects of LPC on the contractions induced by high-K(+) (10-40 mM), UK14,304 (10 approximately 100 nM; a selective alpha(2)-adrenoceptor agonist) and sodium orthovanadate (SOV; 10 microM approximately 3 mM) in endothelium-denuded aortae were compared. Aortic ERK activity and the mRNA expression for GPR4 (a putative LPC receptor) were also measured.
  
  
  RESULTS
  OLETF rats exhibited (vs. age-matched LETO rats): (1) greater potentiation of high-K(+)-induced contraction by 10 microM LPC - a potentiation attenuated by 10 microM genistein, protein tyrosine kinase (PTK) inhibitor, (2) greater potentiation of UK14,304 (10 approximately 100 nM)-induced contractions by LPC (1 microM approximately 10 microM) - a potentiation attenuated by 10 microM genistein, 50 microM tyrphostin A23 (PTK inhibitor) or 10 microM PD98059 (MEK 1/2 inhibitor), (3) greater basal and LPC (1 microM)-induced ERK activities, (4) greater basal and 100 nM UK14,304-stimulated ERK2 activities in both the absence and presence of 10 microM LPC, (5) greater SOV (10 microM approximately 3 mM)-induced contractions, (6) greater potentiation of SOV-induced contractions by 10 microM LPC - a potentiation suppressed by 10 microM PD98059 or 10 microM genistein, (7) upregulation of GPR4 mRNA.
  
  
  CONCLUSIONS
  These results suggest that the LPC-induced potentiation of contractions in the OLETF rat aorta may be attributable to increased PTKs or ERK activity and/or to receptor upregulation.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Kamata
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D011188:Potassium / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D043562:Receptors, G-Protein-Coupled / Q000032:analysis; D015854:Up-Regulation; D014638:Vanadates; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D008244:Lysophosphatidylcholines; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014662:Vasoconstrictor Agents; D014638:Vanadates; D000068438:Brimonidine Tartrate; D017027:Protein Tyrosine Phosphatases; D011188:Potassium