The putative somatostatin antagonist cyclo-somatostatin has opioid agonist effects in gastrointestinal preparations

Rita Benko, Angelina Antwi, Lorand Bartho

Research output: Contribution to journalArticle

3 Citations (Scopus)


Aims: 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. Main methods: 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. Key findings: 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. Significance: 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.

Original languageEnglish
Pages (from-to)728-732
Number of pages5
JournalLife Sciences
Issue number19-20
Publication statusPublished - May 22 2012



  • CYN-154806
  • Cholinergic contractions
  • Cyclo-somatostatin
  • Guinea-pig ileum
  • Naloxone
  • Opioid agonist
  • Rat stomach fundus strip
  • Somatostatin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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