Potent bombesin receptor antagonists distinguish receptor subtypes.
Potent bombesin receptor antagonists distinguish receptor subtypes.
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有效的铃蟾肽受体拮抗剂可区分受体亚型。
DOI：
10.1152/ajpgi.1990.259.3.g468
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Jensen,RT
中科院分区：
文献类型：
--
作者：
vonSchrenck,T;Wang,LH;Coy,DH;Villanueva,ML;Mantey,S;Jensen,RT
为了确定新描述的蛙皮素（BN）受体拮抗剂是否区分BN受体亚型，我们研究了它们与食管肌肉或胰腺腺泡组织上的BN受体相互作用的能力。对于抑制125 I-[Tyr 4]BN与大鼠胰腺组织的结合，相对效力为[D-Phe 6]BN-（6-13）乙酯（5 nM）大于Ac-胃泌素释放肽（GRP）-（20-26）乙酯（17 nM）大于[D-Phe 6，Cpa，14，psi 13-14]BN-（6-14）（40 nM）大于[Leu 14，psi 13-14]BN（0.43 μ M）大于[Tyr 4，D-Phe 12]BN = [D-Pro 4，D-Trp 7，9，10]物质P（SP）-4-11（13 μ M）大于[Leu 14，psi 9，10]BN（32 μ M）大于[D-Arg 1，D-Trp 7，9，Leu 11]SP（70 μ M）。每种拮抗剂还抑制125 I-[Tyr 4]BN或125 I-Bolton-Hunter-neuromedin B与大鼠食管组织的结合，并且每种拮抗剂对每种示踪剂的效力相似。与大鼠胰腺相比，[D-Phe 6]BN-（6-13）乙酯、Ac-GRP-（20-26）乙酯、[D-Phe 6，Cpa 14，psi 13-14]BN-（6-14）、[Leu 14，psi 13-14]BN和[Leu 14，psi 9，10]BN分别具有10，000、2，940、1，425、122和4倍的活性，对BN受体的亲和力较弱。相比之下，[Tyr 4，D-Phe 12]BN、[D-Pro4，D-Trp 7，9，10]SP-4-11和[D-Arg 1，D-Trp 7，9，Leu 11]SP的亲和力分别比胰腺组织高4倍、4倍和9倍。比较每种肽抑制等浓度BN或神经介肽B刺激大鼠食道肌收缩的能力的活性，表明每种肽具有与抑制结合相同的相对效力。（250字处删节）
To determine whether newly described bombesin (BN) receptor antagonists distinguish subtypes of BN receptors, we investigated their abilities to interact with BN receptors on esophageal muscle or pancreatic acinar tissue. For inhibition of binding of 125I-[Tyr4]BN to rat pancreatic tissue, the relative potencies were [D-Phe6]BN-(6-13)ethyl ester (5 nM) greater than Ac-gastrin-releasing peptide (GRP)-(20-26)ethyl ester (17 nM) greater than [D-Phe6,Cpa,14, psi 13-14]BN-(6-14) (40 nM) greater than [Leu14, psi 13-14]BN (0.43 microM) greater than [Tyr4,D-Phe12]BN = [D-Pro4, D-Trp7,9,10]substance P (SP)-4-11 (13 microM) greater than [Leu14, psi 9,10]BN (32 microM) greater than [D-Arg1,D-Trp7,9,Leu11]SP (70 microM). Each antagonist also inhibited binding of 125I-[Tyr4]BN or 125I-Bolton-Hunter-neuromedin B to rat esophageal tissue, and the potency of each antagonist for each tracer was similar. In comparison to rat pancreas, [D-Phe6]BN-(6-13)ethyl ester, Ac-GRP-(20-26)ethyl ester, [D-Phe6,Cpa14, psi 13-14]BN-(6-14), [Leu14, psi 13-14]BN, and [Leu14, psi 9,10]BN had a 10,000-, 2,940-, 1,425-, 122-, and 4-fold, respectively, weaker affinity for BN receptors. In contrast [Tyr4,D-Phe12]BN, [D-Pro4,D-Trp7,9,10]SP-4-11, and [D-Arg1,D-Trp7,9,Leu11]SP had a 4-, 4-, and 9-fold, respectively, higher affinity compared with pancreatic tissue. Comparison of the activity of each peptide at inhibiting the ability of equipotent concentrations of BN or neuromedin B to stimulate contraction of rat esophageal muscle demonstrated that each peptide had the same relative potencies as for inhibiting binding.(ABSTRACT TRUNCATED AT 250 WORDS)