Stoner J, Manganiello V C, Vaughan M
Proc Natl Acad Sci U S A. 1973 Dec;70(12):3830-3. doi: 10.1073/pnas.70.12.3830.
Bradykinin, 1-100 mug/ml, produced a rapid rise in the concentration of 3':5'-guanosine monophosphate (cyclic GMP) and 3':5'-adenosine monophosphate (cyclic AMP) in slices of guinea pig lung. Concentrations of both nucleotides reached a maximum in about 2 min, then declined to a basal levels in 6-12 min. The transient nature of the effect was presumbaly due to the rapid destruction of bradykinin as evidenced by (1) reaccumulation of nucleotides when bradykinin was added a second time, and (2) potentiation of the bradykinin effects by pyroGlu-Lys-Trp-Ala-Pro, a peptide that inhibits inactivation of bradykinin by kininase. It has been reported elsewhere that histamine, prostaglandins E(1) and E(2), and beta-adrenergic stimulation can cause accumulation of cyclic AMP in lung slices without affecting cyclic GMP concentration, whereas acetylcholine increases the concentrations of both cyclic GMP and cyclic AMP. Thus it was possible that the effects of bradykinin were indirect, i.e., secondary to release of one or more of these compounds. Promethazine (an antihistamine), propranolol (a beta-adrenergic blocking agent) and atropine (an anticholinergic agent) did not alter basal cyclic nucleotide concentrations or the effects of bradykinin. Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, which alone were without effect, in the presence of bradykinin completely prevented the rise in cyclic AMP but did not interfere with cyclic GMP accumulation. Similarly, the effect of acetylcholine on cyclic AMP was abolished by indomethacin while that on cyclic GMP was unaltered. We suggest that in lung and probably in other tissues, bradykinin, acetylcholine, and perhaps other stimuli enhance the synthesis and release of prostaglandins as one of the consequences of their effects on cyclic GMP metabolism.
1-100微克/毫升的缓激肽可使豚鼠肺切片中3':5'-鸟苷单磷酸（环鸟苷酸）和3':5'-腺苷单磷酸（环腺苷酸）的浓度迅速升高。两种核苷酸的浓度在约2分钟内达到最大值，然后在6 - 12分钟内降至基础水平。这种效应的短暂性可能是由于缓激肽的快速破坏，证据如下：（1）第二次添加缓激肽时核苷酸重新积累；（2）焦谷氨酸-赖氨酸-色氨酸-丙氨酸-脯氨酸（一种抑制激肽酶使缓激肽失活的肽）增强了缓激肽的作用。其他地方已有报道，组胺、前列腺素E(1)和E(2)以及β-肾上腺素能刺激可导致肺切片中环腺苷酸积累而不影响环鸟苷酸浓度，而乙酰胆碱可增加环鸟苷酸和环腺苷酸的浓度。因此，缓激肽的作用可能是间接的，即继发于这些化合物中一种或多种的释放。异丙嗪（一种抗组胺药）、普萘洛尔（一种β-肾上腺素能阻滞剂）和阿托品（一种抗胆碱能药）既不改变基础环核苷酸浓度，也不改变缓激肽的作用。两种前列腺素合成抑制剂吲哚美辛和阿司匹林，单独使用时无作用，在缓激肽存在时可完全阻止环腺苷酸升高，但不干扰环鸟苷酸积累。同样，吲哚美辛消除了乙酰胆碱对环腺苷酸的作用，而对环鸟苷酸的作用未改变。我们认为，在肺以及可能在其他组织中，缓激肽、乙酰胆碱以及可能的其他刺激物会增强前列腺素的合成和释放，这是它们对环鸟苷酸代谢产生影响的后果之一。
