Severi C, Jensen R T, Erspamer V, D'Arpino L, Coy D H, Torsoli A, Delle Fave G
Gastroenterology Unit, University La Sapienza, Rome, Italy.
Am J Physiol. 1991 May;260(5 Pt 1):G683-90. doi: 10.1152/ajpgi.1991.260.5.G683.
Recent studies suggest that different subtypes of receptors may mediate the action of various bombesin-related peptides in different tissues. In the present study the ability of bombesin and its structurally related peptides [litorin, gastrin-releasing peptide (GRP), GRP18-27, neuromedin B, [Leu8]litorin, and bombesin nonapeptide BN(6-14)] to interact with smooth muscle cells isolated from guinea pig stomach was investigated. Each peptide induced a specific contractile response with potencies (D50 in pM) of [Leu8]litorin (0.7) greater than bombesin (1.2) greater than litorin (3) greater than neuromedin B (3.5) = GRP (3.8) = GRP18-27 (3.9) greater than BN(6-14) (70.9). The specific bombesin receptor antagonist psi 13,14-bombesin differed in its potency for inhibiting equipotent concentrations of bombesin, GRP, or neuromedin B, was equipotent for bombesin or GRP (IC50 12.7 and 22.1 nM), and was 11 times less potent for neuromedin B (IC50 234.5 nM), suggesting the presence of subtypes of receptors mediating the action of bombesin-related peptides. To further investigate this possibility, a technique of receptor protection that enables selective preservation of one receptor type was used. GRP or bombesin protected completely the response to GRP or bombesin but abolished the subsequent contractile response to neuromedin B. Neuromedin B, instead, protected only the response to neuromedin B. These results demonstrate that gastric smooth muscle cells possess specific receptors that interact with bombesin-related peptides and that two receptor subtypes mediate the contractile response to these peptides: one subtype is selective for bombesin or GRP, the other for neuromedin B.
最近的研究表明，不同亚型的受体可能介导不同组织中各种蛙皮素相关肽的作用。在本研究中，研究了蛙皮素及其结构相关肽[促胃液素释放肽（GRP）、GRP18 - 27、神经降压素B、[亮氨酸8]促胃液素释放肽、蛙皮素九肽BN(6 - 14)]与从豚鼠胃中分离出的平滑肌细胞相互作用的能力。每种肽都诱导了一种特异性收缩反应，其效力（半数有效剂量，单位为皮摩尔）为：[亮氨酸8]促胃液素释放肽（0.7）大于蛙皮素（1.2）大于促胃液素释放肽（3）大于神经降压素B（3.5） = GRP（3.8） = GRP18 - 27（3.9）大于BN(6 - 14)（70.9）。特异性蛙皮素受体拮抗剂ψ13,14 - 蛙皮素在抑制等效力浓度的蛙皮素、GRP或神经降压素B时效力不同，对蛙皮素或GRP效力相当（半数抑制浓度分别为12.7和22.1纳摩尔），而对神经降压素B的效力低11倍（半数抑制浓度为234.5纳摩尔），这表明存在介导蛙皮素相关肽作用的受体亚型。为了进一步研究这种可能性，使用了一种能够选择性保留一种受体类型的受体保护技术。GRP或蛙皮素完全保护了对GRP或蛙皮素的反应，但消除了随后对神经降压素B的收缩反应。相反，神经降压素B仅保护对神经降压素B的反应。这些结果表明，胃平滑肌细胞具有与蛙皮素相关肽相互作用的特异性受体，并且两种受体亚型介导对这些肽的收缩反应：一种亚型对蛙皮素或GRP具有选择性，另一种对神经降压素B具有选择性。
