Ca2+-Mobilizing Endothelin-A Receptors Inhibit Voltage-Gated Ca2+ Influx through Gi/oSignaling Pathway in Pituitary Lactotrophs

Tomić, Melanija; Goor, Fredrick Van; He, Miao; Živadinović, Dragoslava; Stojilković, Stanko S.

doi:10.1124/mol.61.6.1329

Cited by 20 publications

(20 citation statements)

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“…Extracellular Cs ϩ in 2-5 mm concentrations fully blocks K ir channels in these cells (37). The addition of 5 mm Cs ϩ had a minor stimulatory effect on basal PRL release but did not affect bromocriptine-induced (Fig.…”

Section: Dopamine Inhibits Ca 2ϩ Transients and Prl Release In Cells mentioning

confidence: 98%

Dopamine Inhibits Basal Prolactin Release in Pituitary Lactotrophs through Pertussis Toxin-Sensitive and -Insensitive Signaling Pathways

González-Iglesias

Murano

et al. 2007

Endocrinology

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Dopamine D2 receptors signal through the pertussis toxin (PTX)-sensitive G(i/o) and PTX-insensitive G(z) proteins, as well as through a G protein-independent, beta-arrestin/glycogen synthase kinase-3-dependent pathway. Activation of these receptors in pituitary lactotrophs leads to inhibition of prolactin (PRL) release. It has been suggested that this inhibition occurs through the G(i/o)-alpha protein-mediated inhibition of cAMP production and/or G(i/o)-betagamma dimer-mediated activation of inward rectifier K(+) channels and inhibition of voltage-gated Ca(2+) channels. Here we show that the dopamine agonist-induced inhibition of spontaneous Ca(2+) influx and release of prestored PRL was preserved when cAMP levels were elevated by forskolin treatment. We further observed that dopamine agonists inhibited both spontaneous and depolarization-induced Ca(2+) influx in untreated but not in PTX-treated cells. This inhibition was also observed in cells with blocked inward rectifier K(+) channels, suggesting that the dopamine effect on voltage-gated Ca(2+) channel gating is sufficient to inhibit spontaneous Ca(2+) influx. However, agonist-induced inhibition of PRL release was only partially relieved in PTX-treated cells, indicating that dopamine receptors also inhibit exocytosis downstream of voltage-gated Ca(2+) influx. The PTX-insensitive step in agonist-induced inhibition of PRL release was not affected by the addition of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and lithium, an inhibitor of glycogen synthase kinase-3, but was attenuated in the presence of phorbol 12-myristate 13-acetate, which inhibits G(z) signaling pathway in a protein kinase C-dependent manner. Thus, dopamine inhibits basal PRL release by blocking voltage-gated Ca(2+) influx through the PTX-sensitive signaling pathway and by desensitizing Ca(2+) secretion coupling through the PTX-insensitive and protein kinase C-sensitive signaling pathway.

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Section: Dopamine Inhibits Ca 2ϩ Transients and Prl Release In Cells mentioning

confidence: 98%

Dopamine Inhibits Basal Prolactin Release in Pituitary Lactotrophs through Pertussis Toxin-Sensitive and -Insensitive Signaling Pathways

González-Iglesias

Murano

et al. 2007

Endocrinology

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“…This signaling molecule acts directly on ion channels, inactivating Ca 2+ channels (25,26) and activating GIRK channels (27). Although there was no evidence for ET-1-mediated Ca 2+ channel inhibition in lactotrophs, ET-1 activated GIRK channels (3,23). Activation of these channels by G i/o βγ leads to membrane hyperpolarization (Fig.…”

mentioning

confidence: 98%

“…ET-1 inhibited Ca 2+ influx through a pertussis toxin (PTX)-sensitive G i/o signaling pathway by activating inward rectifying K + (GIRK) channels, hyperpolarizing the cell (23). The initial rise in [Ca 2+ ] i was mediated by a G protein other than G i/o .…”

mentioning

confidence: 99%

Endothelin Action on Pituitary Lactotrophs: One Receptor, Many GTP-Binding Proteins

et al. 2006

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The secretion of prolactin (PRL) from pituitary lactotrophs of the rat is predominantly under inhibitory control exerted by dopamine (DA) of hypothalamic origin (1). Other PRL-inhibiting substances of hypothalamic origin include somatostatin and endothelin (ET) (2). The latter is the focus of a recent article from the Stojilkovic lab (3) and of this report. In addition to the PRL-inhibiting substances, a host of candidate PRL-releasing hormones, also of hypothalamic origin, exist (2). These include thyrotropin-releasing hormone (TRH), vasoactive intestinal polypeptide, angiotensin II, oxytocin (OT), and even DA itself (2). Each has well-described receptors on the lactotroph membrane and, in most cases, has well-defined postreceptor transduction cascades that regulate PRL secretion. These include the activation of excitatory or inhibitory guanosine triphosphate (GTP)-binding proteins (G proteins) (G s , G q , and G i/o ), which activate or inhibit adenylyl cyclase with downstream effects on adenosine 3′,5′-monophosphate (cAMP) formation or which activate phospholipase C (PLC). Although the nature of these pathways differs, they share one final common denominator: They each regulate PRL secretion by affecting the intracellular levels of calcium, the key ion evoking PRL exocytosis.The ETs are a family of vasoconstrictor peptides that were found in (4) and later purified from tissue culture media of vascular endothelial cells (5). Three different ET isopeptides encoded by three separate genes were identified and designated ET-1, -2, and -3 (6). Similarly, three types of ET receptors have been identified and cloned (7-9). In pituitary cells, endothelins operate through ET A receptors, which have greater affinity for ET-1 and ET-2 than for ET-3 (10). Early evidence suggested that the ETs may affect pituitary hormone secretion. Indeed, their mRNAs are found in the pituitary gland and in hypothalamic magnocellular nuclei (11,12). Moreover, ETs and their receptors are found in the anterior lobe of the pituitary gland (13), and ET-like immunoreactivity is found in lactotrophs, gonadotrophs, and somatotrophs (14). This suggests that the ETs may be autocrine regulators of pituitary hormone secretion (15).Other lines of evidence indicate that the ETs play a role in the secretion of hormones from the anterior pituitary gland. It has been reported that ETs acting at ET A receptors (10) diminish PRL secretion while enhancing luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone secretion in vitro (16)(17)(18). In the presence of DA, the PRL secretory response to ET-1 is biphasic, consisting of an initial rapid high-amplitude stimulatory phase followed by a sustained modest elevation as long as ET-1 is present (19). In the absence of DA, the initial ET-mediated stimulatory response is followed by a sustained inhibition of PRL secretion, which lasts for tens of minutes after the removal of the ET-1 (19). The effect of ET-1 in lactotrophs is partially mediated by the activation of large-conductance Ca ...

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“…It seems that SAL does not act through the dopamine D2 receptors, but utilize receptor independent mechanisms to stimulate PRL High affinity binding sites for this putative PRF have been detected in median eminence where TIDA projects and the NIL that are known terminal fields of THDA/PHDA DAergic systems 2002;Homicsko, 2003). Reserpine pretreatment (blocking VMAT) prevented the effect of SAL on PRL release.…”

Section: Physiology Of Responsiveness: the Balancementioning

confidence: 99%

“…Functional ETA receptors are expressed in all five secretory pituitary cell types included lactotrophs. The ET receptors are connected to both stimulatory and inhibitory (Gs, Gi/o, Gz) G-protein pathways (Tomic, 2002;Andric, 2005).…”

Section: Endothelin Receptorsmentioning

confidence: 99%

The Regulation of Pituitary Prolactin Secretion: Hypothalamic, Intrapituitary and Intracellular Factors and Signaling Mechanisms

Reinhoffer¹,

Márk²,

Vecsernyés³

et al. 2013

Prolactin

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Ca²⁺-Mobilizing Endothelin-A Receptors Inhibit Voltage-Gated Ca²⁺ Influx through G_i/oSignaling Pathway in Pituitary Lactotrophs

Cited by 20 publications

References 44 publications

Dopamine Inhibits Basal Prolactin Release in Pituitary Lactotrophs through Pertussis Toxin-Sensitive and -Insensitive Signaling Pathways

Dopamine Inhibits Basal Prolactin Release in Pituitary Lactotrophs through Pertussis Toxin-Sensitive and -Insensitive Signaling Pathways

Endothelin Action on Pituitary Lactotrophs: One Receptor, Many GTP-Binding Proteins

The Regulation of Pituitary Prolactin Secretion: Hypothalamic, Intrapituitary and Intracellular Factors and Signaling Mechanisms

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