Phorbol esters as probes of the regulation of thyrotropin secretion

Koenig, Ronald J.; Senator, David; Larsen, P. Reed

doi:10.1016/s0006-291x(84)80375-7

Cited by 12 publications

(3 citation statements)

References 9 publications

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“…In many cases, phorbol esters can be shown to enhance evoked transmitter release (Pozzan et al, 1984;Harris et al, 1985;Publicover, 1985;Zurgil and Zisapel, 1985;Eusebi et al, 1986). Furthermore, phorbol esters also augment the secretion of products from non-neuronal cells, such as mast cells and most endocrine and exocrine cells (Kojima et al, 1983;Katakami et al, 1984;Koenig et al, 1984;Yamatani et al, 1985;Ronning and Martin, 1986;Shaw and Hanson, 1986;Stutchfield et al, 1986;Takuma and Ichida, 1986;Hishikawa et al, 1985;Turgeon and Waring, 1986). Effects of phorbol esters on transmitter release from neurons do not appear to be due to an enhancement of voltage-sensitive Ca2+ influx (but see Wakade et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Down regulation of protein kinase C in neuronal cells: effects on neurotransmitter release

et al. 1987

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We investigated the effects of phorbol esters on protein kinase C (PKC) activity and on neurotransmitter release from cultured neuronal cells. Both differentiated and undifferentiated PC12 pheochromocytoma cells contained high levels of protein PKC. Under normal conditions all the enzyme activity was found in the cytoplasm. Addition of the phorbol esters phorbol 12-myristate-13-acetate (TPA) or phorbol 12,13- dibutyrate (PDBu) caused a rapid translocation of PKC from the cytoplasm to the particulate fraction. Continued culture of cells with these phorbol esters resulted in the decline of total PKC activity. After 10–20 hr of culture, both membrane and cytoplasmic PKC activity had declined to background levels. cAMP-dependent and Ca2+/calmodulin- dependent protein kinase activities were only slightly affected by chronic phorbol ester treatment. Addition of active phorbol esters to PC12 cells produced an enhancement of the depolarization-induced release of 3H-norepinephrine. Following chronic phorbol ester treatment, the ability of these substances to enhance evoked catecholamine release was lost. Furthermore, depolarizing stimuli released considerably less 3H-norepinephrine than in control untreated cells. Phorbol esters also enhanced depolarization-induced 3H- norepinephrine release from primary cultures of rat sympathetic neurons. Chronic treatment of these neurons with phorbol esters also resulted in the loss of their ability to enhance transmitter release and in a large reduction in the extent of depolarization-evoked transmitter release. Chronic phorbol ester treatment also resulted in the disappearance of PKC from sympathetic neurons, but had little effect on cAMP-dependent or Ca2+/calmodulin-dependent kinase activities. These results demonstrate that PKC-deficient neurons can be prepared. The data also demonstrate that depolarization-induced neurotransmitter release is mediated by both protein kinase C-dependent and independent pathways.

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Section: Discussionmentioning

confidence: 99%

Down regulation of protein kinase C in neuronal cells: effects on neurotransmitter release

et al. 1987

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“…How might the localization of protein kinase C relate to neuronal function? Phorbol esters influence hormonal release in a variety of peripheral systems (Koenig et al, 1984;Kojima et al, 1983) and enhance transmitter release from adrenal medullary cells (Knight and Baker, 1983;Pozzan et al, 1984). These findings suggest that protein kinase C may also regulate neurotransmitter release in the central nervous system, which could account for the association of [SH]PDBu binding with nerve terminals of certain pathways.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous localization of protein kinase C in rat brain: autoradiographic analysis of phorbol ester receptor binding

Worley¹,

Baraban²,

Snyder³

1986

J. Neurosci.

266

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Protein kinase C is a calcium- and phospholipid-stimulated enzyme present in high concentration in the brain. Phorbol esters are potent tumor promoters that bind to specific receptors with high affinity. Several lines of evidence indicate that the phorbol ester receptor is identical to protein kinase C. To determine the distribution of protein kinase C, we have localized phorbol ester receptors in the rat brain by autoradiography, using [3H]phorbol 12,13-dibutyrate ([3H]PDBu) and have performed a variety of lesions to assess the nature of the cellular elements possessing the binding sites. The [3H]PDBu binding sites in the rat brain are discretely localized and primarily associated with neurons. Evidence is presented for localization to intrinsic neurons of the cortex and hippocampus, terminals of the striatonigral projection, a projection to the molecular layer of the dentate gyrus, and to dendrites of Purkinje cells.

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“…Higher con¬ centrations of ionophores, e.g. 5 pmol/1 or greater, caused hormone secretion (Pressman & Fahim, 1982; Knight & Baker, 1983;Koenig, Senator & Larsen, 1984), but also generated DAG (Kolesnick & Gershengorn, 1984), damaged plasma membranes (Knight & Baker, 1983) and caused intracellular disruption and cell death (Pressman & Fahim, 1982).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D-enhanced thyrotrophin release from rat pituitary cells: effects of Ca2+, dihydropyridines and ionomycin

d’Emden

Wark²

1989

Journal of Endocrinology

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Vitamin D may regulate pituitary function, as there are selective effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on gene expression in clonal pituitary tumour cells, and on TRH-induced TSH release in normal rat pituitary cells in vitro. The role of Ca2+ in 1,25-(OH)2D3-enhanced TSH release from primary rat pituitary cell cultures was investigated. Pretreatment with 10 nmol 1,25-(OH)2D3/l for 24 h augmented KCl (3-60 mmol/l)-induced TSH release over 1 h at all KCl concentrations greater than 7.5 mmol/l (P less than 0.001), with a 76% enhancement of TSH release induced by 30 mmol KCl/l (P less than 0.001). The Ca2+ channel antagonist nifedipine (10 nmol/l-10 mumol/l) caused a concentration-dependent inhibition of KCl (60 mmol/l)-induced TSH secretion. Pretreatment with 1,25-(OH)2D3 enhanced KCl-induced release at all concentrations of nifedipine (P less than 0.001). The Ca2+ selective divalent cation ionophore ionomycin (1 nmol/l-1 mumol/l), and the Ca2+ channel agonist BAY K 8644 (10 nmol/l-1 mumol/l) increased prolactin secretion but did not increase TSH release, and 1,25-(OH)2D3 had no effect. At an extracellular Ca2+ concentration of less than 500 nmol/l, TRH-induced TSH release was observed only after treatment with 1,25-(OH)2D3 (P less than 0.01). As the extracellular Ca2+ concentration was increased, greater increments of TRH-induced TSH release were observed following pretreatment with 1,25-(OH)2D3 (P less than 0.01). However, the effect of 1,25-(OH)2D3 in the thyrotroph was independent of the pretreatment extracellular Ca2+ concentration. We have shown that 1,25-(OH)2D3 acts selectively on the thyrotroph to enhance in-vitro responsiveness to TRH and KCl. These data suggest that the action of 1,25-(OH)2D3 in the thyrotroph is to enhance intracellular signal transduction. They further support a permissive or regulatory role of vitamin D in the normal pituitary gland.

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Phorbol esters as probes of the regulation of thyrotropin secretion

Cited by 12 publications

References 9 publications

Down regulation of protein kinase C in neuronal cells: effects on neurotransmitter release

Down regulation of protein kinase C in neuronal cells: effects on neurotransmitter release

Heterogeneous localization of protein kinase C in rat brain: autoradiographic analysis of phorbol ester receptor binding

Vitamin D-enhanced thyrotrophin release from rat pituitary cells: effects of Ca2+, dihydropyridines and ionomycin

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