Calcium-independent and cAMP-dependent Modulation of Soluble Guanylyl Cyclase Activity by G Protein-coupled Receptors in Pituitary Cells

Kostic, Tatjana S.; Tomić, Melanija; Andrić, Silvana A.; Stojilković, Stanko S.

doi:10.1074/jbc.m112439200

Cited by 22 publications

(17 citation statements)

References 52 publications

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“…Furthermore, here we showed that inhibition of phosphodiesterases by IBMX led to facilitation of pacemaking in somatotrophs. This treatment elevates both cAMP and cGMP concentrations in pituitary cells, reflecting intrinsic activity of adenylyl cyclase and soluble guanylyl cyclase (Kostic et al 2002). In our hands, GHRH also stimulated pacemaking, and it is well established that this agonist enhances cAMP and cGMP production (Kostic et al 2004;Lussier et al 1991;Tomic et al 1999a), which in turn activates TTX-insensitive cation channels that predominantly conduct Na ϩ (Kato and Sakuma 1997;Kato et al 1992;Lussier et al 1991).…”

Section: Discussionmentioning

confidence: 76%

Mechanism of Spontaneous and Receptor-Controlled Electrical Activity in Pituitary Somatotrophs: Experiments and Theory

Tsaneva-Atanasova

Sherman²,

Goor³

et al. 2007

Journal of Neurophysiology

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135

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. Cultured pituitary somatotrophs release growth hormone in response to spontaneous Ca 2ϩ entry through voltage-gated calcium channels (VGCCs) that is governed by plateau-bursting electrical activity and is regulated by several neurohormones, including GH-releasing hormone (GHRH) and somatostatin. Here we combine experiments and theory to clarify the mechanisms underlying spontaneous and receptor-controlled electrical activity. Experiments support a role of a Na ϩ -conducting and tetrodotoxin-insensitive channel in controlling spontaneous and GHRH-stimulated pacemaking, the latter in a cAMP-dependent manner; an opposing role of spontaneously active inwardly rectifying K ϩ (K ir ) channels and G-protein-regulated K ir channels in somatostatin-mediated inhibition of pacemaking; as well as a role of VGCCs in spiking and large conductance (BK-type) Ca 2ϩ -activated K ϩ channels in plateau bursting. The mathematical model is compatible with a wide variety of experimental data involving pharmacology and extracellular ion substitution and supports the importance of constitutively active tetrodotoxin-insensitive Na ϩ and K ir channels in maintaining spontaneous pacemaking in pituitary somatotrophs. The model also suggests that these channels are involved in the up-and downregulation of electrical activity by GHRH and somatostatin. In the model, the plateau bursting is controlled by two functional populations of BK channels, characterized by distance from the VGCCs. The rapid activation of the proximal BK channels is critical for the establishment of the plateau, whereas slow recruitment of the distal BK channels terminates the plateau. I N T R O D U C T I O NIn the absence of hypothalamic factors in vitro, the membrane potential (V m ) of secretory anterior pituitary cells in culture is not stable but oscillates from the baseline potential of about -60 mV. When V m oscillations reach the threshold level, pituitary cells fire action potentials (APs). This is a common feature of all secretory anterior pituitary cell types and is observed in 15-80% of cells, depending on the cell type and preparation Stojilkovic and Catt 1992). The majority of cultured somatotrophs and lactotrophs frequently exhibit broader V m oscillations in the form of a depolarizing plateau with bursts of APs superimposed. These spikes are small in amplitude and usually do not reach 0 mV (Kwiecien et al. 1997;Sims et al. 1991;van Goor et al. 2001a). Such complex plateau bursting activity is periodic and results in an oscillatory increase in intracellular Ca 2ϩ concentration ([Ca 2ϩ

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Section: Discussionmentioning

confidence: 76%

Mechanism of Spontaneous and Receptor-Controlled Electrical Activity in Pituitary Somatotrophs: Experiments and Theory

Tsaneva-Atanasova

Sherman²,

Goor³

et al. 2007

Journal of Neurophysiology

Self Cite

135

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“…Additionally, elevations in cAMP affect exocytosis (Renström et al, 1997; Sikdar et al, 1998; Cochilla et al, 2000; Kostic et al, 2002; Sedej et al, 2005; Gonzalez-Iglesias et al, 2006), but it is less clear exactly which exocytic stages are modulated by cAMP. In lactotrophs, cAMP facilitates hormone release via several mechanisms (Gonzalez-Iglesias et al, 2006, 2008; Stojilkovic et al, 2010), also by affecting the exocytic machinery (Sikdar et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

cAMP-Mediated Stabilization of Fusion Pores in Cultured Rat Pituitary Lactotrophs

et al. 2013

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Regulated exocytosis mediates the release of hormones and transmitters. The last step of this process is represented by the merger between the vesicle and the plasma membranes, and the formation of a fusion pore. Once formed, the initially stable and narrow fusion pore may reversibly widen (transient exocytosis) or fully open (full-fusion exocytosis). Exocytosis is typically triggered by an elevation in cytosolic calcium activity. However, other second messengers, such as cyclic AMP (cAMP), have been reported to modulate secretion. The way in which cAMP influences the transitions between different fusion pore states remains unclear. Here, hormone release studies show that prolactin release from isolated rat lactotrophs stimulated by forskolin, an activator of adenylyl cyclases, and by membrane-permeable cAMP analog (dbcAMP), exhibit a biphasic concentration dependency. While at lower concentrations (2–10 μM forskolin and 2.5–5 mM dbcAMP) these agents stimulate prolactin release, an inhibition is measured at higher concentrations (50 μM forskolin and 10–15 mM dbcAMP). By using high-resolution capacitance (Cm) measurements, we recorded discrete increases in Cm, which represent elementary exocytic events. An elevation of cAMP leaves the frequency of full-fusion events unchanged, while increasing the frequency of transient events. These exhibited a wider fusion pore as measured by increased fusion pore conductance and a prolonged fusion pore dwell-time. The probability of observing rhythmic reopening of transient fusion pores was elevated by dbcAMP. In conclusion, cAMP-mediated stabilization of wide fusion pores prevents vesicles from proceeding to the full-fusion stage of exocytosis, which hinders vesicle content discharge at high cAMP concentrations.

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“…Anterior pituitaries were removed from adult female Sprague-Dawley rats obtained from Tacoma Farms (Germantown, NY, USA) and dispersed as described previously (Kostic et al 2002). Dispersed cells were cultured for 24 h in medium 199 containing Earle's salts, sodium bicarbonate, 10% horse serum, and penicillin (100 U/ml) and streptomycin (100 mg/ml).…”

Section: Cell Culturesmentioning

confidence: 99%

Molecular cloning and characterization of α1-soluble guanylyl cyclase gene promoter in rat pituitary cells

Jiang

Stojilković

2006

Journal of Molecular Endocrinology

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Soluble guanylyl cyclase is a cytosolic enzyme which catalyzes conversion of GTP to the second messenger cyclic GMP. The transcriptional regulation at the promoter levels of four soluble guanylyl cyclase subunits, termed a1, a2, b1, and b2, is largely unknown. In this study, we identified the transcription start site of a1-soluble guanylyl cyclase gene in rat pituitary cells and cloned the 3 . 5 kb 5 0 -promoter. Sequence analysis of this TATA-less promoter revealed the presence of several putative-binding sites for transcriptional factors, including CCAAT site at K41 to K32 and Sp1 site at K34 to K24. Transfection of pituitary cells with constructs of variable lengths confirmed the relevance of different promoter regions in the control of transcriptional activity. Among them, the K49 to C156 region was critical for basal transcriptional activity. Electrophoretic mobility shift assay using nuclear proteins extracted from normal and immortalized pituitary cells indicated that the CCAAT/Sp1 site within the K49 to C156 region was able to specifically interact with CCAAT-binding factor and Sp1. These two sites were partly overlapped and both of them conferred stimulatory effects. The in vivo recruitment of CCAAT-binding factor and Sp1 was confirmed by chromatin immunoprecipitation. These results indicate that the composite CCAAT/Sp1 cis-element contributes to the expression of a1-sGC subunit in resting pituitary cells.

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Calcium-independent and cAMP-dependent Modulation of Soluble Guanylyl Cyclase Activity by G Protein-coupled Receptors in Pituitary Cells

Cited by 22 publications

References 52 publications

Mechanism of Spontaneous and Receptor-Controlled Electrical Activity in Pituitary Somatotrophs: Experiments and Theory

Mechanism of Spontaneous and Receptor-Controlled Electrical Activity in Pituitary Somatotrophs: Experiments and Theory

cAMP-Mediated Stabilization of Fusion Pores in Cultured Rat Pituitary Lactotrophs

Molecular cloning and characterization of α1-soluble guanylyl cyclase gene promoter in rat pituitary cells

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