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Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2

Identifieur interne : 009347 ( Main/Exploration ); précédent : 009346; suivant : 009348

Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2

Auteurs : Seung-Kwon Yang [Australie] ; Helena C. Parkington [Australie] ; Jacques Epelbaum [France] ; Damien J. Keating [Australie] ; CHEN CHEN [Australie]

Source :

RBID : Pascal:07-0328815

Descripteurs français

English descriptors

Abstract

The secretion of growth hormone (GH) is inhibited by hypothalamic somatostatin (SRIF) in somatotropes through five subtypes of the somatostatin receptor (SSTR1-SSTR5). We aimed to characterize the subtype(s) of SSTRs involved in the Ca2+ current reduction in GH3 somatotrope cells using specific SSTR subtype agonists. We used nystatin-perforated patch clamp to record voltage-gated Ca2+ currents, using a holding potential of -80 mV in the presence of K+ and Na+ channel blockers. We first established the presence of T-, L-, N-, and P/Q-type Ca2+ currents in GH3 cells using a variety of channel blockers (Ni+, nifedipine, ω-conotoxin GVIA, and ω-agatoxin IVA). SRIF (200 nM) reduced Land N-type but not T- or P/Q-type currents in GH3 cells. A range of concentrations of each specific SSTR agonist was tested on Ca2+ currents to find the maximal effective concentration. Activation of SSTR2 with 10-7 and 10-8M L-797,976 decreased the voltage-gated Ca2+ current and abolished any further decrease by SRIF. SSTR1, SSTR3, SSTR4, and SSTR5 agonists at 10-7 M did not modify the voltage-gated Ca2+ current and did not affect the Ca2+ current response to SRIF. These results indicate that SSTR2 is involved mainly in regulating voltage-gated Ca2+ currents by SRIF, which contributes to the decrease in intracellular Ca2+ concentration and GH secretion by SRIF.


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Le document en format XML

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<div type="abstract" xml:lang="en">The secretion of growth hormone (GH) is inhibited by hypothalamic somatostatin (SRIF) in somatotropes through five subtypes of the somatostatin receptor (SSTR1-SSTR5). We aimed to characterize the subtype(s) of SSTRs involved in the Ca
<sup>2+</sup>
current reduction in GH3 somatotrope cells using specific SSTR subtype agonists. We used nystatin-perforated patch clamp to record voltage-gated Ca
<sup>2+</sup>
currents, using a holding potential of -80 mV in the presence of K
<sup>+</sup>
and Na
<sup>+</sup>
channel blockers. We first established the presence of T-, L-, N-, and P/Q-type Ca
<sup>2+</sup>
currents in GH3 cells using a variety of channel blockers (Ni
<sup>+</sup>
, nifedipine, ω-conotoxin GVIA, and ω-agatoxin IVA). SRIF (200 nM) reduced Land N-type but not T- or P/Q-type currents in GH3 cells. A range of concentrations of each specific SSTR agonist was tested on Ca
<sup>2+</sup>
currents to find the maximal effective concentration. Activation of SSTR2 with 10
<sup>-7</sup>
and 10
<sup>-8</sup>
M L-797,976 decreased the voltage-gated Ca
<sup>2+</sup>
current and abolished any further decrease by SRIF. SSTR1, SSTR3, SSTR4, and SSTR5 agonists at 10
<sup>-7</sup>
M did not modify the voltage-gated Ca
<sup>2+</sup>
current and did not affect the Ca
<sup>2+</sup>
current response to SRIF. These results indicate that SSTR2 is involved mainly in regulating voltage-gated Ca
<sup>2+</sup>
currents by SRIF, which contributes to the decrease in intracellular Ca
<sup>2+</sup>
concentration and GH secretion by SRIF.</div>
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