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Somatostatin inhibits cAMP-dependent and cAMP-independent calcium influx in the clonal pituitary tumor cell line AtT-20 through the same receptor population

T Reisine, HL Wang and S Guild

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia.

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.

Volume 245, Issue 1, pp. 225-231, 04/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.