title: Somatostatin-induced paradoxical increase in intracellular Ca2+ concentration and insulin release in the presence of arginine vasopressin in clonal HIT-T15 beta-cells.
abstract: Somatostatin, a hormone that signals via G(i)/G(o), usually inhibits increases in intracellular calcium concentration ([Ca(2+)](i)) and insulin release from beta-cells. We have found that in the presence of arginine vasopressin (AVP), which signals via G(q), somatostatin increased [Ca(2+)](i), leading to insulin release in HIT-T15 cells. The increase in [Ca(2+)](i) by somatostatin was observed even after 60 min of AVP treatment. Somatostatin alone failed to increase [Ca(2+)](i) and insulin release. Somatostatin induced changes in [Ca(2+)](i) in a biphasic pattern, characterized by a sharp and transient increase followed by a rapid decline to sub-basal levels. Pretreatment with pertussis toxin, which inactivates G(i)/G(o), abolished the effects of somatostatin. U-73122, an inhibitor of phospholipase C, antagonized the somatostatin-induced increase in [Ca(2+)](i). In Ca(2+)-free medium, somatostatin still increased [Ca(2+)](i). Depletion of intracellular Ca(2+) stores with thapsigargin, a microsomal Ca(2+)-ATPase inhibitor, abolished somatostatin's effect. In the presence of bradykinin, another G(q)-coupled receptor agonist, somatostatin also increased [Ca(2+)](i), but not in the presence of isoproterenol (a G(s)-coupled receptor agonist) or medetomidine (a G(i)/G(o)-coupled receptor agonist). Our findings suggest that somatostatin signals through G(i)/G(o), and involves phospholipase C and Ca(2+) release from the endoplasmic reticulum. The increase in [Ca(2+)](i) by somatostatin leads to insulin release. This cross-talk is specific to G(q) and G(i)/G(o), and is not limited to the AVP and somatostatin receptors.
authors: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011-1250, USA.
authors: Henrique
authors: H
authors: Cheng
authors: Sirintorn
authors: S
authors: Yibchok-Anun
authors: Seung-Chun
authors: SC
authors: Park
authors: Walter H
authors: WH
authors: Hsu
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D010477:Perfusion; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D004963:Estrenes; D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D001127:Arginine Vasopressin; C074854:U 73343; D013004:Somatostatin; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D002118:Calcium