Somatostatin inhibits cAMP-dependent and cAMP-independent calcium influx in the clonal pituitary tumor cell line AtT-20 through the same receptor population.
The characteristics of somatostatin (SRIF) inhibition of calcium influx stimulated by corticotropin releasing factor (CRF), an activator of adenylate cyclase, and K+, a membrane depolarizing agent, in AtT-20 cells were assessed. Changes in cytosolic calcium levels were measured using the fluorescence probe Quin 2. Both CRF and K+ raise cytosolic calcium levels by stimulating calcium influx. SRIF induced an immediate inhibition of CRF and K+-stimulated calcium influx. This effect was concentration-dependent with IC50 values for SRIF's blockade of CRF and K+ stimulation of 64 +/- 13 pM and 100 +/- 15 pM, respectively. The SRIF analogs, SRIF 28, Trp8-SRIF and Tyr11-SRIF had the same rank order of potency to block CRF and K+-induced calcium influx. The inhibitory effects of SRIF on AtT-20 cells were abolished by pertussis toxin pretreatment. SRIF inhibition of both CRF and K+-induced calcium influx desensitized. The desensitization was rapid (T1/2 approximately 2.5 min), dependent on the concentration of SRIF and not due to the degradation of the peptide. The ability of SRIF to block CRF (cyclic AMP-dependent) and K+ (cyclic AMP-independent)-stimulated calcium influx into AtT-20 cells cannot be separated.
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D051379:Mice; D037342:Pertussis Toxin; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000634:Aminoquinolines; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; C035739:Quin2; D011188:Potassium; D002118:Calcium