Imaging of intracellular calcium in rat anterior pituitary cells in response to growth hormone releasing factor.

Kato, Masakatsu; Hoyland, John S.; Sikdar, Sujit Kumar; Mason, William T.

doi:10.1113/jphysiol.1992.sp018997

Cited by 57 publications

(34 citation statements)

References 24 publications

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“…6B). Similar experimental observations have been reported previously (Kato et al 1992;Kwiecien et al 1997;Tomic et al 1999a). Our model therefore incorporates a nonselective, Na ϩ -carrying current termed I NS,Na but not the TTX-sensitive Na ϩ current (Fig.…”

Section: Dependence Of Spontaneous Pacemaking On Extracellular Cationssupporting

confidence: 68%

“…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). Forskolin, an activator of adenylyl cyclase, also stimulates firing of action potentials in pituitary cells (Gonzalez-Iglesias et al 2006a).…”

Section: Discussionmentioning

confidence: 78%

“…GHRH stimulates and SRIF inhibits TTX-insensitive Na ϩ current in a cAMP/protein-kinase-A-dependent manner (Kato and Sakuma 1997). 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%

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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

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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: Dependence Of Spontaneous Pacemaking On Extracellular Cationssupporting

confidence: 68%

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

show abstract

“…] c and hormone release (15,20,22,29). To quantify the responses to the HRHs, we measured the changes of [Ca 2ϩ ] c induced in the different cell types.…”

Section: Stimulation Of Hrh Receptors Induces An Increase Of [Ca 2ϩmentioning

confidence: 99%

Anterior pituitary thyrotropes are multifunctional cells

Alonso

Núñez

García‐Sancho

2004

American Journal of Physiology-Endocrinology and Metabolism

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Anterior pituitary (AP) contains some unorthodox multifunctional cells that store and secrete two different AP hormones (polyhormonal cells) and/or respond to several hypothalamic-releasing hormones (HRHs; multiresponsive cells). Multifunctional cells may be involved in paradoxical secretion (secretion of a given AP hormone evoked by a noncorresponding HRH) and transdifferentiation (phenotypic switch between different mature cell types without cell division). Here we combine calcium imaging (to assess responses to the four HRHs) and multiple sequential immunoassay of the six AP hormones to perform a single-cell phenotypic study of thyrotropes in normal male and female mice. Surprisingly, most of the thyrotropes were polyhormonal, containing, in addition to thyrotropin (TSH), luteinizing hormone (40 -42%) and prolactin (19 -21%). Thyrotropes costoring growth hormone and/or ACTH were found only in females (24% of each type). These results suggest that costorage of the different hormones does not happen at random and that gender favors certain hormone combinations. Our results indicate that thyrotropes are a mosaic of cell phenotypes rather than a single cell type. The striking promiscuity of TSH storage should originate considerable mix-up of AP hormone secretions on stimulation of thyrotropes. However, response to thyrotropin-releasing hormone was much weaker in the polyhormonal thyrotropes than in the monohormonal ones. This would limit the appearance of paradoxical secretion under physiological conditions and suggests that timing of hormone and HRH receptor expression during the transdifferentiation process is finely and differentially regulated. anterior pituitary; hypothalamic releasing factors; paradoxical secretion THE ANTERIOR PITUITARY (AP) contains five main cell types, somatotropes, mammotropes, corticotropes, thyrotropes, and gonadotropes, which secrete growth hormone (GH), prolactin (PRL), ACTH, thyrotropin (TSH), and gonadotropins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)], respectively. Thyrotropes are the least abundant cell type, amounting to ϳ5-8% of all the AP cells. However, this cell type plays a pivotal role in control of metabolism through regulation of thyroid activity. In the classic view, each AP cell type stores a single hormone in which secretion is specifically regulated by a particular hypothalamic-releasing hormone (HRH). Thus thyrotropes are believed to store and release TSH and express functional thyrotropin-releasing hormone (TRH) receptors involved in hypothalamic control of TSH secretion. However, in the last decade, this "one cell-one hormone" hypothesis has been challenged repeatedly. It has been reported, for example, that many pituitary cells may store and release more than one AP hormone. Mammosomatotropes that store and release GH and PRL (13) have been regarded as an intermediate stage for conversion of somatotropes into mammotropes, a phenotypic switch between mature cell types without cell division called transdifferentiation (13, 31). Polyhormona...

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“…Since secretion of AP hormones is triggered by an increase in [Ca¥]é (Gershengorn, 1986;Kato et al 1992;Prevarskaya et al 1994;Kasahara et al 1994), it seems reasonable to conclude that amino acids may stimulate secretion acting directly at the AP cell level. This was confirmed here for prolactin secretion (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms for stimulation of rat anterior pituitary cells by arginine and other amino acids

Alonso

Núñez

García‐Sancho

1997

The Journal of Physiology

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Arginine and other amino acids are secretagogues for growth hormone and prolactin in the intact animal, but the mechanism of action is unclear. We have studied the effects of amino acids on cytosolic free calcium concentration ([Ca2+]i) in single rat anterior pituitary (AP) cells. Arginine elicited a large increase of [Ca2+]i in about 40 % of all the AP cells, suggesting that amino acids may modulate hormone secretion by acting directly on the pituitary. Cell typing by immunofluorescence of the hormone the cells store showed that the arginine‐sensitive cells are distributed uniformly within all the five AP cell types. The arginine‐sensitive cells overlapped closely with the subpopulation of cells sensitive to thyrotrophin‐releasing hormone. Other cationic as well as several neutral (dipolar) amino acids had the same effect as arginine. The increase of [Ca2+]i was dependent on extracellular Ca2+ and blocked by dihydropyridine, suggesting that it is due to Ca2+ influx through l‐type voltage‐gated Ca2+ channels. The [Ca2+]i increase was also blocked by removal of extracellular Na+ but not by tetrodotoxin. The substrate specificity for stimulation of AP cells resembled closely that of the amino acid transport system B0,+. We propose that electrogenic amino acid influx through this pathway depolarizes the plasma membrane with the subsequent activation of voltage‐gated Ca2+ channels and Ca2+ entry. Amino acids also stimulated prolactin secretion in vitro with a similar substrate specificity to that found for the [Ca2+]i increase. Existing data on the stimulation of secretion of other hormones by amino acids suggest that a similar mechanism could apply to other endocrine glands.

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Imaging of intracellular calcium in rat anterior pituitary cells in response to growth hormone releasing factor.

Cited by 57 publications

References 24 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

Anterior pituitary thyrotropes are multifunctional cells

Mechanisms for stimulation of rat anterior pituitary cells by arginine and other amino acids

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