Contraction of the guinea pig isolated, perfused trachea to purine and pyrimidine agonists

JS Fedan, JL Stem and B Day

Physiology Section, National Institute for Occupational Safety and Health, Morgantown, West Virginia.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 268, Issue 3, pp. 1321-1327, 03/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics

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