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First published on March 22, 2005; DOI: 10.1124/mol.104.010470

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Received for publication December 20, 2004.
Revised March 21, 2005.
Accepted for publication March 22, 2005.

Somatostatin increases phospholipase D activity and PIP2 synthesis in clonal {beta}-cells HIT-T15

Henrique Cheng 1, Justin A Grodnitzky 1, Sirintorn Yibchok-anun 1, Jing Ding 1, Walter H Hsu 1*

1 Iowa State University

* Address correspondence to: E-mail: whsu{at}iastate.edu

Abstract

In the presence of arginine vasopressin (AVP), somatostatin (SS) increases [Ca2+]i, leading to a transient increase in insulin release from clonal {beta}-cells HIT-T15 via Gi/o and phospholipase C (PLC) pathway (Cheng et al., 2002a). The present study was to elucidate the mechanisms underlying SS-induced [Ca2+]i increase in the presence of AVP. We found the effect of SS was mediated by {beta}{gamma} subunits, but not by {alpha} subunit of Gi/o. Since SS alone failed to increase [Ca2+]i, we hypothesized that SS increases PIP2 synthesis, providing extra substrate for preactivated PLC-{beta} to generate IP3. SS alone did not increase IP3 levels, but AVP + SS did. SS increased PIP2 levels, but decreased PIP levels. We further hypothesized that PLD mediates SS-induced changes in PIP2 levels. Both the phospholipase D (PLD) inhibitors and antibody vs. PLD1 antagonized AVP-SS-induced increases in [Ca2+]i. PLD inhibitor also antagonized SS-induced increase in PIP2 levels. In addition, SS increased PLD activity. These results suggested that activation of SS receptors that are coupled to the {beta}{gamma}dimer of Gi/o leads to PLD1 activation, thus promoting the synthesis of phosphatidic acid. Since phosphatidic acid activates PIP-5 kinase, this evokes an increase in PIP2 synthesis. The PIP2 generated by SS administration increases substrate for preactivated PLC-{beta}, which hydrolyzes PIP2 to form IP3, leading to an increase in [Ca2+]i. The regulation of PIP2 synthesis by Gi/o-coupled receptors via PLD activation represents a novel signaling mechanism for SS and a novel concept in the crosstalk between Gq- and Gi/o-coupled receptors in {beta}-cells.


Key words: Somatostatin, Vasopressin/Oxytocin, Gi family, Gq/11 family, Phospholipase C's, Phospholipase D's, IP3/DAG, Calcium (G Protein Coupled Signals), Ca imaging, Antibody


This article has been cited by other articles:


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 J. Biol. Chem.Home page
J. A. Grodnitzky, N. Syed, M. J. Kimber, T. A. Day, J. G. Donaldson, and W. H. Hsu
Somatostatin Receptors Signal through EFA6A-ARF6 to Activate Phospholipase D in Clonal beta-Cells
J. Biol. Chem., May 4, 2007; 282(18): 13410 - 13418.
[Abstract] [Full Text] [PDF]


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