title: The putative somatostatin antagonist cyclo-somatostatin has opioid agonist effects in gastrointestinal preparations.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Benko
authors.forename: Angelina
authors.initials: A
authors.lastname: Antwi
authors.forename: Lorand
authors.initials: L
authors.lastname: Bartho
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D005748:Gastric Fundus; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000037:antagonists & inhibitors*
chemical_list: D000701:Analgesics, Opioid; C403089:CYN 154806; D009292:Narcotic Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011957:Receptors, Opioid; D017481:Receptors, Somatostatin; C067675:cyclosomatostatin; D009270:Naloxone; D013004:Somatostatin; D009020:Morphine; D006632:Histamine; D000109:Acetylcholine