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 (T( 1/2 ) ~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.