Liapakis G, Hoeger C, Rivier J, Reisine T
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, USA.
J Pharmacol Exp Ther. 1996 Mar;276(3):1089-94.
Somatostatin (SRIF) induces its biological actions by interacting with a family of five recently cloned receptors. SRIF receptor subtype, SSTR1, has high affinity for SRIF, but no ligand has been available that selectively binds to this receptor. Desamino acid(1,2,5) [DTryptophan8, N-p-isopropl-4-aminomethyl-l-phenylalanine9]SRIF(des-AA1,2,5 [DT rp8, IAmp9]SRIF inhibits the binding of [125ITyr11]SRIF to the cloned human SSTR1 with an affinity of 1.8+0.7nM, but does not bind to the other cloned SRIF receptors. des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF bound selectively, potently and saturably to SSTR1 with a Kd of 0.5 + 0.1 nM and a maximal binding density of 226 +/- 56 fmol/mg of protein. The binding of des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF to SSTR1 was potently inhibited by SRIF, [DTrp8]SRIF, des-AA1,2,5[DTrp8,IAmp9,DSer13]SRIF and SRIF 28 with K, values of 0.7+0.3, 0.2+0.2, 4.3+0.7 and 0.6+0.1 nM, respectively. SRIF analogs that selectively bind to SSTR2 and SSTR5 were impotent in displacing des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF from human SSTR1. des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF binding to SSTR1 expressed in COS-7 cells was reduced by GTPgS, and this effect was prevented by pertussis toxin treatment. In contrast, the binding of[125ITyr11]SRIF to SSTR1 was not affected by these treatments. These findings indicate that des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF may bind to SSTR1 in a defferent manner than SRIF. des-AA1,2,5[DTrp8,IAmp9]SRIF and its tyrosine analog are the first ligands that selectively bind to SSTR1 with high affinity and should be useful in localizing and determining the functional properties of this receptor.
生长抑素（SRIF）通过与最近克隆的五个受体家族相互作用来诱导其生物学作用。SRIF受体亚型SSTR1对SRIF具有高亲和力，但尚无选择性结合该受体的配体。去氨基（1,2,5）[D色氨酸8，N-对异丙基-4-氨甲基-L-苯丙氨酸9] SRIF（des-AA1,2,5 [DTrp8，IAmp9] SRIF）以1.8 + 0.7 nM的亲和力抑制[125I酪氨酸11] SRIF与克隆的人SSTR1的结合，但不与其他克隆的SRIF受体结合。des-AA1,5 [125I酪氨酸2，D色氨酸8，IAmp9] SRIF以0.5 + 0.1 nM的Kd和226 +/- 56 fmol / mg蛋白质的最大结合密度选择性、强效且饱和地结合到SSTR1。des-AA1,5 [125I酪氨酸2，D色氨酸8，IAmp9] SRIF与SSTR1的结合被SRIF、[D色氨酸8] SRIF、des-AA1,2,5 [D色氨酸8，IAmp9，D丝氨酸13] SRIF和SRIF 28有效抑制，其K值分别为0.7 + 0.3、0.2 + 0.2、4.3 + 0.7和0.6 + 0.1 nM。选择性结合SSTR2和SSTR5的SRIF类似物在从人SSTR1上置换des-AA1,5 [125I酪氨酸2，D色氨酸8，IAmp9] SRIF方面无效。GTPγS降低了des-AA1,5 [125I酪氨酸2，D色氨酸8，IAmp9] SRIF与COS-7细胞中表达的SSTR1的结合，百日咳毒素处理可阻止这种作用。相反，[125I酪氨酸11] SRIF与SSTR1的结合不受这些处理的影响。这些发现表明，des-AA1,5 [125I酪氨酸2，D色氨酸8，IAmp9] SRIF与SSTR1的结合方式可能与SRIF不同。des-AA1,2,5 [D色氨酸8，IAmp9] SRIF及其酪氨酸类似物是首批以高亲和力选择性结合SSTR1的配体，应有助于定位和确定该受体的功能特性。
