Griese M, Gobran L I, Rooney S A
Department of Pediatrics, Yale University, School of Medicine, New Haven, Connecticut 06510.
Am J Physiol. 1991 Aug;261(2 Pt 1):L140-7. doi: 10.1152/ajplung.1991.261.2.L140.
Phosphatidylcholine secretion in type II pneumocytes can be stimulated by P1 (adenosine) and P2 (ATP) purinoceptor agonists. The effect of adenosine is mediated by the A2 subtype of the P1 receptor. The A1 subtype is inhibitory. We examined the influence of ATP and the A2 agonist 5'-(N-ethylcarboxyamido)adenosine (NECA) on phosphatidylcholine secretion in primary cultures of rat type II cells. The stimulatory effects of ATP and NECA were less than additive, suggesting a common mechanism of action. NECA and ATP both caused a rapid increase in cAMP, and the combination enhanced this even further. ATP promoted inositol trisphosphate (IP3) formation, whereas NECA did not. The effect of ATP on adenosine 3',5'-cyclic monophosphate (cAMP) but not on IP3 was abolished by a P1 antagonist, and such antagonists diminished its effect on secretion by as much as 75%. The potency orders of ATP analogues in increasing formation of cAMP and IP3 were different. The effects of the ATP analogues on phosphatidylcholine secretion were also inhibited by the P1 antagonists, with the greatest degree of inhibition being observed with the analogue that increased cAMP to the greatest extent. The effect of ATP on secretion was not diminished by either adenosine deaminase (previous data) or AMP deaminase showing that the effects of ATP were not mediated by its metabolism to the P1 agonists adenosine or AMP. These data show that ATP acts at both A2 and P2 receptors but that most of its effects on phosphatidylcholine secretion are mediated by the A2 receptor.
II型肺细胞中的磷脂酰胆碱分泌可被P1（腺苷）和P2（ATP）嘌呤受体激动剂刺激。腺苷的作用由P1受体的A2亚型介导。A1亚型具有抑制作用。我们研究了ATP和A2激动剂5'-（N-乙基甲酰胺基）腺苷（NECA）对大鼠II型细胞原代培养物中磷脂酰胆碱分泌的影响。ATP和NECA的刺激作用小于相加作用，提示存在共同的作用机制。NECA和ATP均导致cAMP迅速增加，二者联合使用时这种增加更为明显。ATP促进肌醇三磷酸（IP3）的形成，而NECA则无此作用。P1拮抗剂可消除ATP对腺苷3',5'-环磷酸单酯（cAMP）的作用，但不影响其对IP3的作用，且此类拮抗剂可将其对分泌的作用降低多达75%。ATP类似物增加cAMP和IP3形成的效价顺序不同。P1拮抗剂也可抑制ATP类似物对磷脂酰胆碱分泌的作用，其中增加cAMP程度最大的类似物受到的抑制程度最高。腺苷脱氨酶（既往数据）或AMP脱氨酶均未减弱ATP对分泌的作用，表明ATP的作用不是通过其代谢为P1激动剂腺苷或AMP介导的。这些数据表明，ATP作用于A2和P2受体，但它对磷脂酰胆碱分泌的大多数作用是由A2受体介导的。
