UTP and diadenosine tetraphosphate accelerate wound healing in the rabbit cornea.
Nucleotides are naturally occurring substances present in tear film that can stimulate tear secretion in animals and humans. We investigated whether certain nucleotides can affect the rate of wound healing in the cornea of white rabbits. In the absence of any added compound, the rate of healing was 72.4 +/- 2.2 microm h(-1). Of all the tested nucleotides, UTP and Ap(4)A were the most active ones, maximally increasing the rate of healing to 121.6 +/- 3.7 and 93.7 +/- 3.2 microm h(-1), respectively. Responses to UTP were dose dependent. UTP had a pD(2) value of 8.9 +/- 0.1 (EC(50): 1.25 nM). P2 purinoceptor antagonists such as suramin and reactive blue-2, inhibited the effect of UTP indicating the involvement of P2Y receptors. Mitogen-activated protein kinase (MAPK) cascade inhibitors also abolished the effects of UTP, suggesting that P2Y receptors are coupled to the MAPK cascade, and that this is involved in controlling the rate of epithelial cell migration.
Pintor
Jesús
J
Departamento de Bioquímica, Escuela Universtaria de Optica, Universidad Complutense de Madrid, c/Arcos de Jalon s/n, Madrid 28037, Spain. jpintor@vet.ucm.es
Bautista
Alfredo
A
Carracedo
Gonzalo
G
Peral
Assumpta
A
D000818:Animals; D003315:Cornea / Q000187:drug effects; D065306:Corneal Injuries; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000293:injuries; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009711:Nucleotides / Q000494:pharmacology; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits; D015398:Signal Transduction; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D015226:Dinucleoside Phosphates; D009711:Nucleotides; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; C020733:diadenosine tetraphosphate; D020928:Mitogen-Activated Protein Kinases; D014544:Uridine Triphosphate