Gobran L I, Rooney S A
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Am J Physiol. 1997 Feb;272(2 Pt 1):L187-96. doi: 10.1152/ajplung.1997.272.2.L187.
ATP stimulation of surfactant secretion in type II cells is mediated by both a P2Y2 receptor coupled to phospholipase C and a receptor coupled to adenylate cyclase. UTP also activates the P2Y2 receptor but does not stimulate adenosine 3',5'-cyclic monophosphate (cAMP) formation. We have examined surfactant secretion and signaling parameters in response to ATP and UTP in type II cells from newborn rats. There was a developmental increase in the response to both agonists. However, whereas ATP increased secretion as early as day 1, the effect of UTP did not become significant until 4 days after birth. ATP increased cAMP formation as early as day 1 but did not promote diacylglycerol formation or phospholipase D activation until day 4. Thus the adenylate cyclase-coupled ATP signaling mechanism is functional early in development but the P2Y2 pathway is not. We therefore used type II cells from 1- to 2-day-old rats to investigate the adenylate cyclase-coupled mechanism in the absence of interactions with the P2Y2 system. Effects of ATP and 5'-(N-ethylcarboxamido)adenosine (NECA) on surfactant secretion and cAMP formation were not additive, and their effects on secretion were antagonized by the same adenosine receptor antagonists. Overnight culture of the cells with NECA almost completely abolished the subsequent increase in cAMP formation in response to NECA, adenosine, and ATP but not to terbutaline. These data suggest that ATP, NECA, and adenosine activate the same receptor. Effects of ATP were not decreased by adenosine deaminase, showing that they are not mediated by adenosine acting directly at adenosine receptors. We suggest that ATP directly activates an adenosine receptor on the type II cell.
三磷酸腺苷（ATP）对II型细胞表面活性物质分泌的刺激作用是由与磷脂酶C偶联的P2Y2受体和与腺苷酸环化酶偶联的受体共同介导的。尿苷三磷酸（UTP）也可激活P2Y2受体，但不会刺激3',5'-环磷酸腺苷（cAMP）的形成。我们研究了新生大鼠II型细胞对ATP和UTP的表面活性物质分泌及信号转导参数。对这两种激动剂的反应均有发育性增加。然而，ATP早在出生第1天就增加了分泌，而UTP的作用直到出生后4天才变得显著。ATP早在第1天就增加了cAMP的形成，但直到第4天才促进二酰基甘油的形成或磷脂酶D的激活。因此，与腺苷酸环化酶偶联的ATP信号转导机制在发育早期就有功能，但P2Y2途径并非如此。因此，我们使用1至2日龄大鼠的II型细胞来研究在不存在与P2Y2系统相互作用的情况下与腺苷酸环化酶偶联的机制。ATP和5'-(N-乙基甲酰胺基)腺苷（NECA）对表面活性物质分泌和cAMP形成的作用并非相加性的，并且它们对分泌的作用被相同的腺苷受体拮抗剂所拮抗。用NECA对细胞进行过夜培养几乎完全消除了随后对NECA、腺苷和ATP而非特布他林的cAMP形成增加。这些数据表明ATP、NECA和腺苷激活相同的受体。腺苷脱氨酶并未降低ATP的作用，表明它们不是由直接作用于腺苷受体的腺苷介导的。我们认为ATP直接激活II型细胞上的腺苷受体。
