Håkanson R, Leander S, Asano N, Feng D M, Folkers K
Department of Pharmacology, University of Lund, Sweden.
Regul Pept. 1990 Oct 29;31(1):75-82. doi: 10.1016/0167-0115(90)90197-5.
Two undecapeptide substance P (SP) analogues, Spantide I and Spantide II, were tested for their capacity to block the contractile effect of SP on the guinea pig isolated taenia coli and the contractile effect of electrical stimulation of the rabbit isolated (and atropinized) iris sphincter, and for their capacity to mobilize histamine from rat isolated peritoneal mast cells. Spantide I and Spantide II have one feature in common, namely D-tryptophan in positions 7 and 9. Spantide I: D-Arg, Pro2, Lys3, Pro4, Gln5, Gln6, D-Trp7, Phe8, D-Trp9, Leu10, Leu11-NH2. Spantide II: D-NicLys1, Pro2, 3-Pal3, Pro4, D-Cl2Phe5, Asn6, D-Trp7, Phe8, D-Trp9, Leu10, Nle11-NH2. Both Spantide I and II were found to be competitive antagonists to SP on the taenia coli and to be capable of blocking the electrically induced non-cholinergic contraction of the iris sphincter. Spantide II had higher pA2 value (taenia coli) than Spantide I, 7.7 versus 7.0, and higher pIC50 value (blockade of tachykinin-mediated neurotransmission in iris sphincter), 6.0 versus 5.1. Both Spantide I and II mobilized histamine from rat peritoneal mast cells but Spantide II was less effective. Spantide I and II were tested for antagonistic specificity. Both blocked contractions of the taenia induced by SP and neurokinin A. In the concentration used, Spantide II in addition blocked the response to neurokinin B. The contractions induced by carbachol, 5-hydroxytryptamine, histamine and prostaglandins (F2 alpha and E1) were not affected; the contractile response to bombesin was inhibited by Spantide I but not by Spantide II.
对两种十一肽P物质（SP）类似物，即Spantide I和Spantide II，进行了测试，以考察它们阻断SP对豚鼠离体结肠带收缩作用以及电刺激兔离体（且已用阿托品处理）虹膜括约肌收缩作用的能力，同时也测试了它们从大鼠离体腹膜肥大细胞中释放组胺的能力。Spantide I和Spantide II有一个共同特征，即在第7和第9位为D-色氨酸。Spantide I：D-精氨酸、Pro2、Lys3、Pro4、Gln5、Gln6、D-色氨酸7、苯丙氨酸8、D-色氨酸9、亮氨酸10、亮氨酸11-氨基。Spantide II：D-尼克赖氨酸1、Pro2、3-棕榈酸3、Pro4、D-氯苯丙氨酸5、天冬酰胺6、D-色氨酸7、苯丙氨酸8、D-色氨酸9、亮氨酸10、正亮氨酸11-氨基。结果发现，Spantide I和II在结肠带上均为SP的竞争性拮抗剂，且能够阻断虹膜括约肌的电诱导非胆碱能收缩。Spantide II在结肠带上的pA2值（7.7）高于Spantide I（7.0），在阻断虹膜括约肌中速激肽介导的神经传递方面的pIC50值（6.0）也高于Spantide I（5.1）。Spantide I和II均能从大鼠腹膜肥大细胞中释放组胺，但Spantide II的效果较差。对Spantide I和II进行了拮抗特异性测试。二者均能阻断SP和神经激肽A诱导的结肠带收缩。在所使用的浓度下，Spantide II还能阻断对神经激肽B的反应。卡巴胆碱、5-羟色胺、组胺和前列腺素（F2α和E1）诱导的收缩未受影响；蛙皮素诱导的收缩反应被Spantide I抑制，但未被Spantide II抑制。
