PURINOCEPTOR CONTROL OF SURFACTANT SECRETION

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This proposal is based on our recent identification and expression of a cDNA specific for a lung P2-purinoceptor. This proposal represents the first description of cloning of a P2-purinoceptor in any system. We will now test the hypothesis that P2-purinoceptors in the lung regulate secretion of surfactant phospholipid necessary for normal lung function and that expression and maturation of these receptors is temporally and hormonally regulated in the perinatal period. The specific aims of the present proposal will be to complete the nucleotide sequence of the cDNAs encoding human and rat Type II cell P2-purinoceptors. Permanent cell lines expressing the Type II cell P2-purinoceptor will be generated and utilized to study hormonal regulation of the receptor. Antisense cRNA probes will be utilized for in situ hybridization to determine cell- specific and ontogenic expression of the Type II cell P2-purinoceptor in lung. Finally, antisense oligodeoxynucleotides and P2-purinoceptor antibodies will be generated and utilized to demonstrate the relationship of P2-purinoceptor expression to regulation of surfactant phospholipid secretion. These studies seek to define for the first time the nature of P2-purinoceptors and controls involved in regulation of P2- purinoceptor expression in the lung. Further knowledge of the structure and ontogenic regulation of P2-purinoceptors in the lung will be valuable in developing new strategies for therapy of lung diseases.