Article date: February 2001
By: Forbes Alderton, Tai‐Ping D Fan, Patrick P A Humphrey in Volume 132, Issue 3, pages 760-766
Somatostatin and the stable octapeptide analogues, octreotide and angiopeptin, were examined for their ability to stimulate the release of tritium from [3H]‐arachidonic acid pre‐loaded CHO‐K1 cells expressing human recombinant sst2, sst3 or sst5 receptors.
Somatostatin stimulated tritium release (pEC50) through the sst2 (7.8±0.1) and sst5 (7.3±0.2), but not the sst3 receptor. Octreotide behaved as a full (sst2 receptor) or partial agonist (sst5 receptor), whereas angiopeptin behaved as a weak partial agonist at both receptor types.
Maximum responses to somatostatin through both receptor types were significantly reduced by pertussis toxin, whereas pEC50 estimates were unaffected.
Inhibition of MEK1 or Src, but not PKA, PI 3‐kinases or tyrosine kinases, by reportedly selective inhibitors reduced sst2‐mediated responses by somatostatin, but not angiopeptin. A selective inhibitor of PKC (Ro‐31‐8220) reduced both somatostatin and angiopeptin responses.
These data provide further evidence for partial agonist activity of synthetic peptides of somatostatin. Furthermore, the somatostatin receptor signalling mechanisms which mediate arachidonic acid mobilization appear to be multiple and complex.
Somatostatin and the stable octapeptide analogues, octreotide and angiopeptin, were examined for their ability to stimulate the release of tritium from [3H]‐arachidonic acid pre‐loaded CHO‐K1 cells expressing human recombinant sst2, sst3 or sst5 receptors.
Somatostatin stimulated tritium release (pEC50) through the sst2 (7.8±0.1) and sst5 (7.3±0.2), but not the sst3 receptor. Octreotide behaved as a full (sst2 receptor) or partial agonist (sst5 receptor), whereas angiopeptin behaved as a weak partial agonist at both receptor types.
Maximum responses to somatostatin through both receptor types were significantly reduced by pertussis toxin, whereas pEC50 estimates were unaffected.
Inhibition of MEK1 or Src, but not PKA, PI 3‐kinases or tyrosine kinases, by reportedly selective inhibitors reduced sst2‐mediated responses by somatostatin, but not angiopeptin. A selective inhibitor of PKC (Ro‐31‐8220) reduced both somatostatin and angiopeptin responses.
These data provide further evidence for partial agonist activity of synthetic peptides of somatostatin. Furthermore, the somatostatin receptor signalling mechanisms which mediate arachidonic acid mobilization appear to be multiple and complex.
British Journal of Pharmacology (2001) 132, 760–766; doi:10.1038/sj.bjp.0703862
DOI: 10.1038/sj.bjp.0703862
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