Somatostatin, a hormone that signals via Gi/Go, usually inhibits increases in intracellular calcium concentration ([Ca2+]i) and insulin release from β-cells. We have found that in the presence of arginine vasopressin (AVP), which signals via Gq, somatostatin increased [Ca2+]i, leading to insulin release in HIT-T15 cells. The increase in [Ca2+]i by somatostatin was observed even after 60min of AVP treatment. Somatostatin alone failed to increase [Ca2+]i and insulin release. Somatostatin induced changes in [Ca2+]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 Gi/Go, abolished the effects of somatostatin. U-73122, an inhibitor of phospholipase C, antagonized the somatostatin-induced increase in [Ca2+]i. In Ca2+-free medium, somatostatin still increased [Ca2+]i. Depletion of intracellular Ca2+ stores with thapsigargin, a microsomal Ca2+-ATPase inhibitor, abolished somatostatin's effect. In the presence of bradykinin, another Gq-coupled receptor agonist, somatostatin also increased [Ca2+]i, but not in the presence of isoproterenol (a Gs-coupled receptor agonist) or medetomidine (a Gi/Go-coupled receptor agonist). Our findings suggest that somatostatin signals through Gi/Go, and involves phospholipase C and Ca2+ release from the endoplasmic reticulum. The increase in [Ca2+]i by somatostatin leads to insulin release. This cross-talk is specific to Gq and Gi/Go, and is not limited to the AVP and somatostatin receptors.

This content is only available as a PDF.
You do not currently have access to this content.