Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Hungary.
Life Sci. 2012 May 22;90(19-20):728-32. doi: 10.1016/j.lfs.2012.03.007. Epub 2012 Mar 28.
Specificity of receptor antagonists used is crucial for clarifying physiological/pathophysiological roles of the respective endogenous agonist. We studied the effects (somatostatin antagonist and possibly other actions) of cyclo-somatostatin (CSST), a putative somatostatin receptor antagonist on the guinea-pig small intestine, a preparation where somatostatin causes inhibition of nerve-mediated contractions.
In isolated organ experiments, half-maximal cholinergic "twitch" contractions of the guinea-pig small intestine were evoked or tonic contractions of the rat stomach fundus strip (in the presence of physostigmine) were elicited by electrical field stimulation. The effects of somatostatin (somatostatin-14), CSST, naloxone, as well as of direct smooth muscle stimulants were examined.
Somatostatin (10 nM-1 μM) caused transient inhibition of the twitch contraction, in a naloxone-insensitive manner. Surprisingly, CSST (0.3-1 μM) also inhibited twitch contractions (more than 50% reduction at 1 μM). This effect was prevented by the opioid receptor antagonist naloxone. Responses to acetylcholine or histamine were not or only minimally inhibited by CSST (up to 3 μM). CSST (0.3 μM in the absence or 1-10 μM in the presence of naloxone) failed to inhibit the effect of somatostatin. The SST(2) receptor antagonist CYN-154806 (3 μM) attenuated the effect of somatostatin and failed to evoke naloxone-sensitive inhibition of the twitch response. The naloxone-sensitive inhibitory effect of CSST on cholinergic contractions was also confirmed in the rat stomach fundus preparation.
Cyclo-somatostatin exerts opioid agonist activity in the two preparations tested, while it does not behave as a somatostatin-receptor antagonist in the guinea-pig intestine.
受体拮抗剂的特异性对于阐明内源性激动剂的生理/病理生理作用至关重要。我们研究了环-生长抑素（CSST）（一种假定的生长抑素受体拮抗剂）对豚鼠小肠的影响（可能还有其他作用），在该制剂中，生长抑素会抑制神经介导的收缩。
在离体器官实验中，通过电刺激诱发豚鼠小肠的半最大胆碱能“抽搐”收缩，或在毒扁豆碱存在的情况下诱发大鼠胃底条带的紧张性收缩。检查了生长抑素（生长抑素-14）、CSST、纳洛酮以及直接平滑肌刺激剂的作用。
生长抑素（10 nM-1 μM）以纳洛酮不敏感的方式引起抽搐收缩的短暂抑制。令人惊讶的是，CSST（0.3-1 μM）也抑制抽搐收缩（在 1 μM 时抑制超过 50%）。这种作用被阿片受体拮抗剂纳洛酮所阻止。CSST（0.3 μM 时无作用，或 1-10 μM 时存在纳洛酮）对乙酰胆碱或组胺的反应没有或仅有轻微抑制（最高 3 μM）。CSST（0.3 μM 时无作用或 1-10 μM 时存在纳洛酮）未能抑制生长抑素的作用。SST（2）受体拮抗剂 CYN-154806（3 μM）减弱了生长抑素的作用，并且未能引起纳洛酮敏感的抽搐反应抑制。CSST 对胆碱能收缩的纳洛酮敏感抑制作用也在大鼠胃底制剂中得到了证实。
环-生长抑素在两种被测试的制剂中表现出阿片样激动剂活性，而在豚鼠肠中它不作为生长抑素受体拮抗剂。
