SSTR2 mediates the somatostatin-induced increase in intracellular Ca 2+ concentration and insulin secretion in the presence of arginine vasopressin in clonal h-cell HIT-T15 Henrique Cheng a , Sirintorn Yibchok-anun a , David H. Coy b , Walter H. Hsu a, * a Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA b Peptide Research Labs, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA Received 13 November 2001; accepted 1 February 2002 Abstract The effects of somatostatin (SRIF) are mediated through the seven transmembrane receptor family that signals via Gi/Go. To date, five distinct SRIF receptors have been characterized and designated SSTR1-5. We have characterized the SRIF receptor that mediates the increase in [Ca 2+ ] i and insulin secretion in HIT-T15 cells (Simian virus 40-transformed Syrian hamster islets) using high affinity, subtype selective agonists for SSTR1 (L-797,591), SSTR2 (L-779,976), SSTR3 (L-796,778), SSTR4 (L-803,087), SSTR5 (L-817,818) and PRL-2903, a specific SSTR2 antagonist. In the presence of arginine vasopressin (AVP), SRIF increased [Ca 2+ ] i and insulin secretion. Treatment with the SSTR2 agonist L-779,976 resulted in similar responses to SRIF. In addition, L-779,976 increased both [Ca 2+ ] i and insulin secretion in a dose-dependent manner. Treatment with L-779,976 alone did not alter [Ca 2+ ] i or basal insulin secretion. In the presence of AVP, all other SRIF receptor agonists failed to increase [Ca 2+ ] i and insulin secretion. The effects of SRIF and L-779,976 were abolished by the SSTR2 antagonist PRL- 2903. Our results suggest that the mechanism underlying SRIF-induced insulin secretion in HIT-T15 cells be mediated through the SSTR2. D 2002 Elsevier Science Inc. All rights reserved. Keywords: SRIF; SSTR2; Intracellular Ca 2+ ; Insulin secretion; HIT-T15 Introduction Somatostatin (SRIF), a tetradecapeptide hormone that has diverse physiological actions, was initially isolated and identified as an inhibitor of growth hormone secretion from anterior pituitary cells [1]. 0024-3205/02/$ - see front matter D 2002 Elsevier Science Inc. All rights reserved. PII:S0024-3205(02)01774-5 * Corresponding author. Tel.: +1-515-294-6864; fax: +1-515-294-2315. E-mail address: whsu@iastate.edu (W.H. Hsu). www.elsevier.com/locate/lifescie Life Sciences 71 (2002) 927 – 936