title: Effects of extracellular triphosphate nucleotides and nucleosides on airway smooth muscle cell proliferation.
abstract: Extracellular ATP and uridine triphosphate (UTP) have a range of effects on a wide variety of cells through the activation of P(2) receptors. The aim of this work was to establish if stimulation with ATP and UTP enhances airway smooth muscle (ASM) cell proliferation and to determine the type of receptor mediating this effect. Proliferation of rat ASM cells was assessed through bromodeoxyuridine (BrdU) uptake and by cell counting. At concentrations of 10(-6) and 10(-5) M, ATP and UTP induced significant increases in BrdU incorporation. ATP analogs specific for the P(2X) and P(2Y1) receptor subtypes had no effect. UDP (a P(2Y6) receptor agonist) produced significant decreases in BrdU incorporation and cell counts. Adenosine, the metabolite of ATP, produced an increase in cell proliferation through stimulation of the A(1) receptor. A(2) and A(3) receptor stimulation had no effect. Reverse transcription and polymerase chain reaction analysis showed that mRNA transcripts for the P(2Y2), P(2Y4), P(2Y6), A(1), A(2), and A(3) receptor subtypes were present in cultured ASM cells. These data show that extracellular UTP, ATP, and their metabolites may affect airway remodeling by increasing or by reducing (P(2Y6) receptor) ASM cell proliferation.
authors.affiliation: Meakins-Christie Laboratories and Montreal Chest Institute Research Center, McGill University, Montreal, Quebec, Canada. Marie-Claire.Michoud@McGill.ca
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Michoud
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Napolitano
authors.forename: Karim
authors.initials: K
authors.lastname: Maghni
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Govindaraju
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cogo
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000166:cytology*; D014544:Uridine Triphosphate / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate