Submitted on June 30, 2003
Accepted on February 9, 2004
P2Y purine receptor responses and expression in the pulmonary circulation of juvenile rabbits
Girija G. Konduri1*, Ivane Bakhuthushvili1, Recia Frenn1, Indira Chandrasekhar1, Elizabeth R. Jacobs2, and Ashwani K. Khanna2
1 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, none
2 Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, none; Department of Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, none
* To whom correspondence should be addressed. E-mail: gkonduri{at}mcw.edu.
The purine nucleotide, ATP mediates pulmonary vasodilation at birth by stimulation of P2Y purine receptors in pulmonary circulation. The specific P2Y receptors in the pulmonary circulation and the segmental distribution of their responses remain unknown. We investigated the effects of purine nucleotides, ATP, ADP and AMP and pyrimidine nucleotides, UTP, UDP and UMP in juvenile rabbit pulmonary arteries for functional characterization of P2Y receptors. We also studied the expression of P2Y receptor subtypes in pulmonary arteries and the role of NO, prostaglandins and cytochrome P450 metabolites in the response to ATP. In the conduit size arteries, ATP ADP and AMP caused greater relaxation responses than UTP, UDP and UMP. In the resistance vessels, ATP and UTP caused comparable vasodilation. Response to ATP was attenuated by P2y antagonist, cibacron blue, NOS antagonist L-NAME and P450 inhibitor, 17-ODYA, but not by P2x antagonist, alpha-beta-methylene ATP or cyclooxygenase inhibitor, indomethacin in the conduit arteries. In the resistance vessels, L-NAME caused a more complete inhibition of the responses to ATP and UTP. Responses to AMP and UMP were NO- and endothelium dependent, whereas, responses to ADP and UDP were NO- and endothelium independent in the conduit arteries. RT-PCR showed expression of P2Y1, P2Y2 and P2Y4, but not P2Y6 receptors in lung parenchyma, pulmonary arteries and pulmonary artery endothelial cells. These data suggest that distinct P2Y receptors mediate the vasodilator responses to purine and pyrimidine nucleotides in the juvenile rabbit pulmonary circulation. ATP appears to cause NO-mediated vasodilation predominantly through P2Y2 receptors on endothelium.
