The Pivotal Role of Phosphoinositide-3 Kinase in the Human Somatostatin sst4 Receptor-Mediated Stimulation of p44/p42 Mitogen-Activated Protein Kinase and Extracellular Acidification

• Published in: Biochemical and biophysical research communications 1999-09, Vol.263 (1), p.239-243
• Main Authors: Smalley, Keiran S.M., Feniuk, Wasyl, Sellers, Lynda A., Humphrey, Patrick P.A.
• Format: Article
• Language: English
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1351

We have previously demonstrated in CHO-K1 cells expressing recombinant human sst4 receptors that somatostatin-induced increases in extracellular acidification are susceptible to a marked desensitisation after pretreatment with somatostatin, but not the somatostatin analogue, L-362855. In the present study, we have examined the human sst4 receptor-mediated stimulation of p44/p42 mitogen-activated protein (MAP) kinase to determine whether this response is susceptible to a similar agonist-specific desensitisation. Western analysis using phosphospecific antibodies revealed that both somatostatin and L-362855 induced a transient stimulation of MAP kinase which could be desensitised by pretreatment with somatostatin, but not L-362855. The selective phosphoinositide (PI) 3-kinase inhibitor, LY 249002, blocked both the somatostatin-induced increase in MAP kinase phosphorylation and extracellular acidification. However, the MEK1 inhibitor, PD 98059, blocked only the sst4 receptor-mediated stimulation of MAP kinase and not the extracellular acidification response. In summary, the human sst4 receptor is selectively desensitised by somatostatin and not by L-362855 and signals through two different PI 3-kinase linked pathways.