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      Inhibitory Control of Growth Hormone Secretion by Somatostatin in Rat Pituitary GC Cells: sst 2 but Not sst 1 Receptors Are Coupled to Inhibition of Single-Cell Intracellular Free Calcium Concentrations

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          Rat pituitary tumor cells (GC cells) exhibit spontaneous oscillations of intracellular free calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>) that allow continuous release of growth hormone (GH). Of the somatostatin (SRIH) receptor subtypes (sst receptors) mediating SRIH action, sst<sub>1</sub> and sst<sub>2</sub> receptors are highly expressed by GC cell membranes. In the present study, the effects of sst<sub>1</sub> or sst<sub>2</sub> receptor activation on single-cell [Ca<sup>2+</sup>]<sub>i</sub> were investigated in GC cells by confocal fluorescence microscopy. In addition, the effects of sst<sub>1</sub> or sst<sub>2</sub> receptor activation on GH secretion were also studied. Our results demonstrate that SRIH decreases [Ca<sup>2+</sup>]<sub>i</sub> baseline and almost completely blocks Ca<sup>2+</sup> transients through activation of sst<sub>2</sub> but not of sst<sub>1</sub> receptors. In contrast, SRIH effectively inhibits GH secretion through activation of both sst<sub>1</sub> and sst<sub>2</sub> receptors. Blocking Ca<sup>2+</sup> transients is less efficient than SRIH to inhibit GH release. The cyclic octapeptide, CYN-154806, antagonizes sst<sub>2</sub> receptors at [Ca<sup>2+</sup>]<sub>i</sub> since it abolishes the sst<sub>2</sub> receptor-mediated inhibition of [Ca<sup>2+</sup>]<sub>i</sub> without affecting single-cell Ca<sup>2+</sup> signals. On the other hand, CYN-154806 alone potently inhibits GH secretion through the involvement of pertussis toxin-sensitive G proteins. In conclusion, the present results demonstrate that SRIH inhibition of GH release in GC cells involves mechanisms either dependent or independent on SRIH modulation of [Ca<sup>2+</sup>]<sub>i</sub>. The implications of CYN-154806 inhibition of GH secretion are discussed.

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          Most cited references 9

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          Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry.

          Nonpeptide agonists of each of the five somatostatin receptors were identified in combinatorial libraries constructed on the basis of molecular modeling of known peptide agonists. In vitro experiments using these selective compounds demonstrated the role of the somatostatin subtype-2 receptor in inhibition of glucagon release from mouse pancreatic alpha cells and the somatostatin subtype-5 receptor as a mediator of insulin secretion from pancreatic beta cells. Both receptors regulated growth hormone release from the rat anterior pituitary gland. The availability of high-affinity, subtype-selective agonists for each of the somatostatin receptors provides a direct approach to defining their physiological functions.
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            Growth hormone secretagogue actions on the pituitary gland: multiple receptors for multiple ligands?

             C. Chen (2000)
            1. Growth hormone (GH) secretion is thought to occur under the reciprocal regulation of two hypothalamic hormones, namely GH-releasing hormone (GHRH) and somatostatin (SRIF), through their engagement with specific cell-surface receptors on the anterior pituitary somatotropes. 2. In addition to GHRH and SRIF, synthetic GH-releasing peptides (GHRP) or GH secretagogue(s) (GHS) regulate GH release through the activation of a novel receptor, the GHS receptor (GHS-R). 3. The cloning of the GHS-R from human, swine and rat identifies a novel G-protein-coupled receptor involved in the control of GH secretion and supports the existence of an undiscovered hormone that may activate this receptor. 4. Varieties of intracellular signalling systems are suggested to mediate the action of GHS, which include changes in intracellular free Ca2+ ([Ca2+]i), cAMP, protein kinases A and C, phospholipase C etc. 5. With regard to the use of signalling systems by GHS, especially a new form of GHRP or GHRP-2, a clear species difference has been demonstrated, supporting the possibility of more than one type of GHS-R.
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              Potent Somatostatin Undecapeptide Agonists Selective for Somatostatin Receptor 1 (sst1)


                Author and article information

                S. Karger AG
                August 2002
                08 August 2002
                : 76
                : 2
                : 99-110
                aDepartment of Physiology and Biochemistry ‘G. Moruzzi’, University of Pisa, Italy, and bU549 INSERM, Paris, France
                64424 Neuroendocrinology 2002;76:99–110
                © 2002 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 46, Pages: 12
                Regulation of Growth Hormone


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