Contraction of the Guinea Pig Isolated, Perfused Trachea to Purine and Pyrimidine Agonists

Details

• Personal Author:
  Day, Brian ; Fedan, Jeffery S. ; Stem JL
• Description:
  Unlike methacholine and histamine, ATP and uridine 5'-triphosphate (UTP) are more potent contractile agonists when they are applied to the mucosal (intraluminal, IL) surface of the guinea pig perfused trachea than when they are applied to the serosal (extraluminal, EL) surface. The relative contractile activities of a series of purine and pyrimidine compounds were assessed. The order of EL activity was: [2-methythio ATP (2 MeSATP) = adenosine 5'-diphosphate (ADP)] > [adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) = ATP = adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S)] > [(beta, gamma-imido ATP) (APPNP) = alpha, beta-methylene ATP (APCPP)] > [UTP = uridine 5'-diphosphate (UDP) = inosine 5'-triphosphate (ITP)] > [xanthosine 5'-triphosphate (XTP) beta, gamma-methylene ATP (APPCP)]. EL adenosine, adenosine 5'-monophosphate, uridine 5'-monophosphate and uridine were weak or inactive. The EL order of activity, therefore, shares some characteristics of P2Y receptors. The order of IL activity was: (ATP = UTP = ITP) > (ATP gamma S = ADP = APPNP = 2 MeSATP) > (UDP = ADP beta S = XTP) > APCPP; the other compounds were weak or inactive. The IL order of activity, therefore, resembled that for P2U or "nucleotide receptors." ATP, APPNP, UTP, UDP, ITP and XTP were more active when added to the IL than after administration to the EL bath; the remaining compounds were similarly active EL and IL, or were more active EL than IL. Greater IL than EL activity of agonists was a property associated with preference for P2U-receptors. The EL and IL activities of the agonists compare favorably with those reported for basolateral and apical stimulation of short circuit current and [Ca++]1 of human respiratory epithelium, and phospholipase C activation of cultured human airway epithelium. [Description provided by NIOSH]
• Subjects:
  Musculoskeletal System Occupational Health Respiratory System Safety
• Keywords:
  Cell Function Cellular Function In Vitro Study Muscle Function Pharmacology Respiratory Function
• ISSN:
  0022-3565
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  268
• Issue:
  3
• NIOSHTIC Number:
  nn:20049832
• Citation:
  J Pharmacol Exp Ther 1994 Mar; 268(3):1321-1327
• Federal Fiscal Year:
  1994
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Pharmacology and Experimental Therapeutics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cb4eca4140191a9bf2a37d6e725078b54335d05d14ebe363b4d22df76c9b376bd711c2b7b51c7829e0d355c14e2912cbaa473776236e8d14dde667f0a7d41925
• Download URL:
  https://stacks.cdc.gov/view/cdc/210452/cdc_210452_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]