AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 5 625-L633, Copyright © 1994 by American Physiological Society
P2u purinoceptor stimulation of surfactant secretion coupled to phosphatidylcholine hydrolysis in type II cells
L. I. Gobran, Z. X. Xu, Z. Lu and S. A. Rooney
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520.
ATP is known to stimulate surfactant phospholipid secretion in type II
cells, and there is evidence that this effect is mediated by a P2
purinoceptor. At least five subtypes of the P2 receptor have been reported,
but it is not clear which one exists on the type II cell. To determine
whether it is the P2u subtype, at which UTP is equipotent with ATP, we have
compared the effects of ATP and UTP on phosphatidylcholine secretion and
second messenger formation in primary cultures of rat type II cells. ATP
and UTP were equally potent in stimulating phosphatidylcholine secretion
and phospholipase D activation. The potency order, UTP = ATP > ADP >
2-methylthio-ATP, was the same as that reported for the P2u receptor. UTP
stimulated diacylglycerol and phosphatidic acid formation to the same
extent as ATP. ATP also increased choline formation. Formation of
diacylglycerol was biphasic, and the first peak in response to ATP was
previously shown to be associated with inositol trisphosphate formation.
Northern analysis showed that the P2u receptor gene was expressed to a
greater extent in type II cells than in whole lung. These data suggest that
ATP and UTP act via a P2u receptor that is coupled to
phosphoinositide-specific phospholipase C with subsequent activation of
phospholipase D acting on phosphatidylcholine. ATP has also been reported
to act at an additional type II cell receptor coupled to adenylate cyclase.
In contrast, UTP did not promote adenosine 3',5'-cyclic monophosphate
formation and therefore does not act at that receptor.
