Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells

Yamashita, Naohide; Kojima, Ichiro; Shibuya, Naohiko; Ogata, Etsuro

doi:10.1152/ajpendo.1987.253.1.e28

Cited by 22 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations are consistent with a view that the ␣-subunit of these proteins inhibits adenylyl cyclase, and the ␤/␥ dimer stimulates K ir channels (Wickman and C lapham, 1995). Somatotrophs also express G-protein-regulated K ir channels, the activation of which by somatostatin hyperpolarizes the cell membrane (Yamashita et al, 1987;Yatani et al, 1987;Mollard et al, 1988;Sims et al, 1991). As shown here, ET-1 activates these channels like somatostatin, but it is not as effective.…”

Section: Discussionsupporting

confidence: 91%

Expression of Ca²⁺-Mobilizing Endothelin_AReceptors and Their Role in the Control of Ca²⁺Influx and Growth Hormone Secretion in Pituitary Somatotrophs

et al. 1999

View full text Add to dashboard Cite

The expression and coupling of endothelin (ET) receptors were studied in rat pituitary somatotrophs. These cells exhibited periods of spontaneous action potential firing that generated high-amplitude fluctuations in cytosolic calcium concentration ([Ca 2ϩ ] i ). The message and the specific binding sites for ET A , but not ET B , receptors were found in mixed pituitary cells and in highly purified somatotrophs. The activation of these receptors by ET-1 led to an increase in inositol 1,4,5-trisphosphate production and the associated rise in [Ca 2ϩ ] i and growth hormone (GH) secretion. The Ca 2ϩ -mobilizing action of ET-1 lasted for 2-3 min and was followed by an inhibition of action potential-driven Ca 2ϩ influx and GH secretion to below the basal levels. As in somatostatin-treated cells, the ET-1-induced inhibition of spontaneous electrical activity and Ca 2ϩ influx was accompanied by the inhibition of adenylyl cyclase and by the stimulation of inward rectifier potassium current. In contrast to somatostatin, ET-1 did not inhibit voltage-gated Ca 2ϩ channels. During prolonged agonist stimulation a gradual recovery of Ca 2ϩ influx and GH secretion occurred. In somatotrophs treated with pertussis toxin overnight, the ET-1-induced Ca 2ϩ -mobilizing phase was preserved, but it was followed immediately by facilitated Ca 2ϩ influx and GH secretion. Both somatostatin-and ET-1-induced inhibitions of adenylyl cyclase activity were abolished in pertussis toxin-treated cells. These results indicate that the transient cross-coupling of Ca 2ϩ -mobilizing ET A receptors to the G i /G o pathway in somatotrophs provides an effective mechanism to change the rhythm of [Ca 2ϩ ] i signaling and GH secretion during continuous agonist stimulation. Key words: somatotrophs; growth hormone; calcium; endothelin; somatostatin; electrical activityAction potential (AP)-driven C a 2ϩ influx through voltage-gated calcium channels (VGCC s) is operative in various endocrine and neuroendocrine cells, including pituitary somatotrophs. Because many different ionic channels act in concert to control AP firing, this pathway is referred to as the membrane potential (V m )-dependent pathway for C a 2ϩ signaling (Stojilkovic, 1998). Several of the ionic channels contributing to the V m pathway in somatotrophs have been identified. These include VGCCs, voltage-gated sodium channels, pacemaker and ATP-gated cationic channels, and several types of potassium channels, including inwardly rectif ying potassium channels (K ir ) (Lewis et al., 1988;Sims et al., 1991;Brake et al., 1994;Koshimizu et al., 1998). Although resting somatotrophs have a fluctuating V m , Kwiecien and colleagues (1997) have found that these pacemaker fluctuations were unable to initiate spontaneous APs in a majority of cultured somatotrophs. Consequently, they suggested that somatotrophs behave as "conditional pacemakers," because the activation of adenylyl cyclase-coupled receptors is required for AP generation. However, others have observed spontaneous APs (Sims et al., 1991) a...

show abstract

Section: Discussionsupporting

confidence: 91%

Expression of Ca²⁺-Mobilizing Endothelin_AReceptors and Their Role in the Control of Ca²⁺Influx and Growth Hormone Secretion in Pituitary Somatotrophs

et al. 1999

View full text Add to dashboard Cite

show abstract

“…It was revealed that SRIF hyperpolarized the [2,6,14,20,22,23]. A similar membrane hyperpolarization has been reported in neurons [4,13] and atrial cells [10].…”

Section: Discussionsupporting

confidence: 79%

“…In human pituitary GH-producing cells, SRIF hyperpolarizes the membrane and thereby inhibits Ca2+-dependent spontaneous action potentials [22]. This membrane hyperpolarization is caused by a G-protein coupled K+ conductance increase [20,23]. A similar membrane hyperpolarization or K+ conductance increase has been reported in primary cultured rat somatotrophs, and clonal rat GH cells [2,6,14].…”

supporting

confidence: 57%

Simultaneous Measurement of Changes in the Membrane Potential and the Intracellular Ca2+ Concentration Caused by Somatostatin in Human GH-Producing Pituitary Tumor Cells.

et al. 1992

View full text Add to dashboard Cite

“…Potential roles of VGCCs and voltage-gated K ϩ channels in GHRH actions have also been suggested (Chen and Clarke 1995;Xu et al 1999), as well as a role of K ir channels (Sims et al 1991), and L-type Ca 2ϩ channels (Kato 1995) in SRIF actions. In immortalized pituitary cells, it has been suggested that SRIF inhibits electrical activity through stimulation of BK channel activity by protein dephosphorylation (White et al 1991), activation of K ir channels (Takano et al 1997) and/or delayed rectifying K ϩ channels (Mollard et al 1988;Yamashita et al 1987), and inhibition of VGCCs (Lewis et al 1986;Luini et al 1986;Mollard et al 1988). …”

Section: Introductionmentioning

confidence: 99%

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

Tsaneva-Atanasova

Sherman²,

Goor³

et al. 2007

Journal of Neurophysiology

135

View full text Add to dashboard Cite

. 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

show abstract

Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells

Cited by 22 publications

References 18 publications

Expression of Ca²⁺-Mobilizing Endothelin_AReceptors and Their Role in the Control of Ca²⁺Influx and Growth Hormone Secretion in Pituitary Somatotrophs

Expression of Ca²⁺-Mobilizing Endothelin_AReceptors and Their Role in the Control of Ca²⁺Influx and Growth Hormone Secretion in Pituitary Somatotrophs

Simultaneous Measurement of Changes in the Membrane Potential and the Intracellular Ca2+ Concentration Caused by Somatostatin in Human GH-Producing Pituitary Tumor Cells.

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

Contact Info

Product

Resources

About

Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells

Cited by 22 publications

References 18 publications

Expression of Ca2+-Mobilizing EndothelinAReceptors and Their Role in the Control of Ca2+Influx and Growth Hormone Secretion in Pituitary Somatotrophs

Expression of Ca2+-Mobilizing EndothelinAReceptors and Their Role in the Control of Ca2+Influx and Growth Hormone Secretion in Pituitary Somatotrophs

Simultaneous Measurement of Changes in the Membrane Potential and the Intracellular Ca2+ Concentration Caused by Somatostatin in Human GH-Producing Pituitary Tumor Cells.

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

Contact Info

Product

Resources

About

Expression of Ca²⁺-Mobilizing Endothelin_AReceptors and Their Role in the Control of Ca²⁺Influx and Growth Hormone Secretion in Pituitary Somatotrophs

Expression of Ca²⁺-Mobilizing Endothelin_AReceptors and Their Role in the Control of Ca²⁺Influx and Growth Hormone Secretion in Pituitary Somatotrophs