Anti-secretory properties of non-peptide somatostatin receptor agonists in isolated rat colon: luminal activity and possible interaction with P-glycoprotein

British Journal of Pharmacology
P T J EmeryG Warhurst

Abstract

1. The diverse physiological actions of somatostatin are mediated by a family of G-protein coupled receptors (SSTRs). Several peptide analogues of somatostatin such as octreotide have been developed for therapeutic use, including treatment of gastrointestinal disorders such as secretory diarrhoea. However, their development as anti-diarrhoeal agents has been limited by poor oral bioavailability, necessitating parenteral administration. This in vitro study investigated the anti-secretory potential of a group of novel, non-peptide, somatostatin-receptor agonists that selectively activate specific SSTR subtypes to assess their potential for oral administration. 2. The ability of the agonists to inhibit forskolin-stimulated chloride secretion was measured using a sensitive bioassay system in isolated rat colonic mucosa. 3. The SSTR-2 selective agonist, L-779,976 was 10-times more potent than octreotide as an inhibitor of secretion when added to the basolateral surface of rat colon. Non-peptide agonists selective for SSTR1 (L-797,591), SSTR3 (L-796,778), SSTR4 (L-803,087) or SSTR5 (L-817,818) showed little or no anti-secretory activity in this preparation. 4. L-779,976 was able to inhibit secretion when applied to the luminal surfac...Continue Reading

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Citations

Sep 28, 2012·Zhurnal evoliutsionnoĭ biokhimii i fiziologii·A O Shpakov
Dec 17, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jaime Pei Pei FoongJoel C Bornstein
Jul 10, 2008·Expert Opinion on Drug Metabolism & Toxicology·Sophie Vallette, Omar Serri
Jul 16, 2010·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·J P P FoongJ C Bornstein
Nov 26, 2009·Therapeutic Advances in Gastroenterology·Alexandru GamanBraden Kuo
Nov 4, 2008·Molecular and Cellular Biochemistry·Kannikar WongdeeNarattaphol Charoenphandhu
Nov 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·R H StephensG Warhurst
Aug 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuji SaitaYasuaki Shimizu
Jul 8, 2020·Tropical Medicine and Infectious Disease·Farzana AfrozeDavid Nalin
Sep 26, 2003·Biochimica Et Biophysica Acta·Lars Neisig MøllerJens Juul Holst

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