Contraction of the guinea pig isolated, perfused trachea to purine and pyrimidine agonists
Fedan, J.S.; Stem, J.L.; Day, B.
Journal of Pharmacology and Experimental Therapeutics 268(3): 1321-1327
1994
ISSN/ISBN: 0022-3565 PMID: 8138946 Document Number: 438757
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-methylthio ATP (2 MeSATP) = adenosine 5'-diphosphate (ADP)) gt (adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) = ATP = adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S)) gt ((beta,gamma-imido ATP) (APPNP) = alpha,beta-methylene ATP (APCPP)) gt (UTP = uridine 5'-diphosphate (UDP) = inosine 5'-triphosphate (ITP)) gt (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 P-2Y receptors. The order of IL activity was: (ATP = UTP = ITP) gt (ATP-gamma-S = ADP = APPNP = 2 MeSATP) gt (UDP = ADP-beta-S = XTP) gt APCPP; the other compounds were weak or inactive. The IL order of activity, therefore, resembled that for P-2U 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 P-2U-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++)-i of human respiratory epithelium, and phospholipase C activation of cultured human airway epithelium.