Growth Hormone Releasing Hexapeptide (GHRP-6) Activates the Inositol (1,4,5)-Trisphosphate/Diacylglycerol Pathway in Rat Anterior Pituitary Cells

Mau, Søren Mads; Witt, Michael-Robin; Bjerrum, Ole J.; Særmark, T.; Vilhardt, Hans

doi:10.3109/10799899509045223

Cited by 34 publications

(20 citation statements)

References 20 publications

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“…In the present investigation, U73122 decreased the transient increase in [Ca 2+ ] i evoked by L-585. Consistent with activation of this pathway were the observations that GHRP-6 and non-peptidergic GHS increased phosphoinositide turnover, and caused translocation of protein kinase C (Adams et al 1995, Mau et al 1995. The activation and interplay of several pathways of signal transduction mediate the effect of GHS in mobilizing Ca 2+ , cAMP, protein kinase A and C, and phospholipase C (Smith et al 1997, Muller et al 1999.…”

Section: Casupporting

confidence: 51%

Mechanism of action of the growth hormone secretagogue, L-692,585, on isolated porcine somatotropes

Glavaski-Joksimovic¹,

Jeftinija²,

Jeremić³

et al. 2002

Journal of Endocrinology

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The effects of a GH secretagogue, L-692,585 (L-585), and human GH-releasing hormone (hGHRH) on calcium transient and GH release were investigated in isolated porcine pituitary cells using calcium imaging and the reverse hemolytic plaque assay (RHPA). Somatotropes were functionally identified by the application of hGHRH. All cells that responded to hGHRH responded to L-585 application. Perfusion application of 10 µM hGHRH and L-585 for 2 min resulted in an increase in intracellular calcium concentrations ([Ca 2+ ] i ) of 53 1 nM (mean S.E.M.) (P<0·01) and 68 2 nM (P<0·01) respectively. The L-585 response was characterized by an initial increase in [Ca )-GRF (1-29) amide) decreased the stimulatory effect of hGHRH. These failed to block the stimulatory effect of L-585, suggesting a different receptor for L-585 from the GHRH receptor. The hGHRHinduced calcium transients and initial peak increase induced by L-585 were significantly decreased by removal of calcium from the bathing medium or the addition of nifedipine, an L-calcium channel blocker. The plateau component of L-585-induced calcium change was abolished by removal of calcium and nifedipine. These results suggest an involvement of calcium channels in GH release. Either SQ-22536, an adenylate cyclase inhibitor, or U73122, a phospholipase C (PLC) inhibitor, blocked the stimulatory effects of hGHRH and L-585 on [Ca 2+ ] i transient, indicating the involvement of adenylate cyclasecAMP and PLC-inositol triphosphate pathways. These results further suggested that calcium mobilization from internal stores during the first phase of the L-585 response induced an increase in [Ca 2+ ] i whereas calcium influx during the second phase is a consequence of somatotrope depolarization.

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Section: Casupporting

confidence: 51%

Mechanism of action of the growth hormone secretagogue, L-692,585, on isolated porcine somatotropes

Glavaski-Joksimovic¹,

Jeftinija²,

Jeremić³

et al. 2002

Journal of Endocrinology

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“…The fulllength sequence of this receptor was identified by using the expression-cloning strategy in Xenopus oocytes. Activation of GHS-R induces a transient increase in the concentration of intracellular calcium in somatotrophs (Bresson-Bepoldin & Dufy-Barbe, 1994), the increase in the level of inositol trisphosphate (IP3) (Mau et al, 1995) and activity of protein kinase-C (PKC) (Cheng et al, 1991).…”

Section: Discovery Of Ghs-rmentioning

confidence: 99%

Ghrelin, a Gastric Hormone with Diverse Functions

Li¹,

Luo²,

Li³

et al. 2012

Chemical Biology

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“…In rat somatotrophs, GHS could induce the accumulation of inositol triphosphate (IP 3 ) and activate protein kinase C (PKC) leading to an increase of intracellular calcium concentration ([Ca 2þ ] i ) [18,19]. On the other hand, the action of GHS on ovine somatotrophs was found to depend mainly on the production of cAMP in which activation of PKC potentiates the protein kinase A (PKA) cascade causing GH secretion [20].…”

Section: Introductionmentioning

confidence: 99%

Signal transduction mechanism of the seabream growth hormone secretagogue receptor

Chan¹,

Leung²,

Wise³

et al. 2004

FEBS Letters

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We have recently cloned the full-length cDNAs of the two growth hormone secretagogue receptor (GHSR) subtypes from a teleost species, the black seabream (Acanthopagrus schlegeli) [Mol. Cell. Endocrinol. 214 (2004) ] i ), whereas sbGHSR-1b appeared to play an inhibitory role on the signal transduction activity of sbGHSR-1a. In the present study, we have further investigated the signal transduction mechanism of sbGHSR-1a. The peptide GHS GHRP-6 and the non-peptide GHS L163,540 were able to trigger a receptor specific and phospholipase C (PLC)-dependent elevation of [Ca 2+ ] i in HEK293 cells stably expressing sbGHSR-1a. This GHS-induced calcium mobilization was also dependent on protein kinase C activated L-type calcium channel opening. It was found that sbGHSR-1a could function in an agonist-independent manner as it exhibited a high basal activity of inositol phosphate production in the absence of GHS, indicating that the fish receptor is constitutively active. In addition, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) were found to be activated upon stimulation of sbGHSR-1a by GHRP-6. This observation provides direct evidence in the coupling of sbGHSR-1a to ERK1/2 activation. Neither G s nor G i proteins are coupled to the receptor, as GHS did not induce cAMP production nor inhibit forskolin-stimulated cAMP accumulation in the sbGHSR-1a bearing cells. Furthermore, the ability of the GHSR antagonist D D -Lys(3)-GHRP-6 to inhibit basal PLC and basal ERK1/2 activity suggests that this compound is an inverse agonist. In summary, the sbGHSR-1a appears to couple through the G q=11 -mediated pathway to activate PLC, resulting in increased IP 3 production and Ca 2+ mobilization from both intracellular and extracellular stores. Moreover, sbGHSR-1a may trigger multiple signal transduction cascades to exert its physiological functions.

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Growth Hormone Releasing Hexapeptide (GHRP-6) Activates the Inositol (1,4,5)-Trisphosphate/Diacylglycerol Pathway in Rat Anterior Pituitary Cells

Cited by 34 publications

References 20 publications

Mechanism of action of the growth hormone secretagogue, L-692,585, on isolated porcine somatotropes

Mechanism of action of the growth hormone secretagogue, L-692,585, on isolated porcine somatotropes

Ghrelin, a Gastric Hormone with Diverse Functions

Signal transduction mechanism of the seabream growth hormone secretagogue receptor

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