Somatostatin receptor-mediated arachidonic acid mobilization: evidence for partial agonism of synthetic peptides

1. Somatostatin and the stable octapeptide analogues, octreotide and angiopeptin, were examined for their ability to stimulate the release of tritium from [(3)H]-arachidonic acid pre-loaded CHO-K1 cells expressing human recombinant sst(2), sst(3) or sst(5) receptors. 2. Somatostatin stimulated tritium release (pEC(50)) through the sst(2) (7.8+/-0.1) and sst(5) (7.3+/-0.2), but not the sst(3) receptor. Octreotide behaved as a full (sst(2) receptor) or partial agonist (sst(5) receptor), whereas angiopeptin behaved as a weak partial agonist at both receptor types. 3. Maximum responses to somatostatin through both receptor types were significantly reduced by pertussis toxin, whereas pEC(50) estimates were unaffected. 4. Inhibition of MEK1 or Src, but not PKA, PI 3-kinases or tyrosine kinases, by reportedly selective inhibitors reduced sst(2)-mediated responses by somatostatin, but not angiopeptin. A selective inhibitor of PKC (Ro-31-8220) reduced both somatostatin and angiopeptin responses. 5. 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.