Pituitary adenylate cyclase-activating polypeptide induces gene expression of the catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine β hydroxylase, through 3′, 5′-cyclic adenosine monophosphate- and protein kinase C-dependent mechanisms in cultured porcine adrenal medullary chromaffin cells

Isobe, Kazumasa; Yukimasa, Nobuyasu; Nakai, Toshiaki; Takuwa, Yoh

doi:10.1016/s0143-4179(96)90084-0

Cited by 36 publications

(23 citation statements)

References 21 publications

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“…Forskolinactivation of the PKA pathway, for example, induces TH, DBH and PNMT expression in cultured bovine chromaffin cells (Stachowiak et al 1990;Hwang et al 1994;Hwang et al 1997) and TH and DBH expression in rat pheochromocytoma-derived PC12 cells (Lewis et al 1983;Kim et al 1994a). Similarly, phorbol ester-activation of PKC has also been shown to increase TH, DBH, and PNMT expression in bovine chromaffin cells (Wan et al 1991;Stachowiak et al 1994;Isobe et al 1996). In addition, interaction between PKA and PKC signaling mechanisms has been reported for the regulation of the TH (Piech-Dumas et al 2001) and DBH PC12 cells were transfected with the wild-type constructs pGL3RP893 or pGL3RP392 or constructs containing mutations in the )168 bp (pGL3RP893mutSp1A or pGL3RP392mutSp1A), ) 48 bp (pGL3RP 893mutSp1B or pGL3RP392mutSp1B) or both (pGL3RP893 mutsp1A/B and pGL3RP392mutSp1A/B) Sp1 sites.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, when these signaling pathways are activated in cultured adrenal chromaffin cells by forskolin (Stachowiak et al 1990;Hwang et al 1994;Hwang et al 1997) or phorbol esters (Wan et al 1991;Stachowiak et al 1994;Isobe et al 1996), respectively, PNMT expression increases. Forskolin and phorbol esters similarly increase PNMT promoter-driven luciferase activity in PC12 and PC12-derived RS1 cells transfected with PNMT promoter-luciferase reporter gene constructs (Morita et al 1995;Tai et al 2001).…”

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confidence: 99%

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Protein kinase A and protein kinase C signaling pathway interaction in phenylethanolamine N‐methyltransferase gene regulation

Tai

Wong

2003

Journal of Neurochemistry

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The protein kinase A (PKA) and protein kinase C (PKC) signaling pathways appear to interact in regulating phenylethanolamine N-methyltransferase (PNMT) promoter-driven gene transcription in PC12 cells. Forskolin treatment of cells transfected with the rat PNMT promoter-luciferase reporter gene construct pGL3RP893 increased promoter activity approximately two-fold whereas phorbol-12-myristate-13 acetate (PMA) treatment had no effect. However, simultaneous forskolin and PMA treatment synergistically activated the PNMT promoter approximately four-fold, suggesting that PKC stimulation requires prior induction of the PKA pathway. Consistent with this possibility the adenylate cyclase inhibitor MDL12,330A, and the PKA inhibitor H-89 prevented PNMT promoter stimulation by the combination of forskolin and PMA. PKA and PKC regulation seems to be mediated in part by Egr-1 and Sp1 through their consensus elements in the PNMT promoter. Forskolin and PMA treatment of PC12 cells increased Egr-1 protein and phosphorylated Egr-1/DNAbinding complex formation to the same extent but only increased phosphorylated Sp1/DNA binding complex formation without altering Sp1 protein levels. Mutation of the ) 165 bp Egr-1 and ) 48 bp Sp1 sites, respectively, attenuated and abolished combined forskolin and PMA-mediated promoter activation. PNMT promoter analysis further showed that synergistic stimulation by PKA and PKC involves DNA sequences between ) 442 and ) 392 bp, and potentially a GCM binding element lying within this region.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Protein kinase A and protein kinase C signaling pathway interaction in phenylethanolamine N‐methyltransferase gene regulation

Tai

Wong

2003

Journal of Neurochemistry

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“…A variety of factors, including neural impulses, have been reported to regulate the TH gene expression in adrenal medullary cells (8)(9)(10). The expression of the TH gene has also been studied in rat pheochromocytoma cell lines (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas

Isobe

Nakai²,

Yukimasa³

et al. 1998

European Journal of Endocrinology

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Objective: To understand the molecular mechanisms by which catecholamine synthesis is controlled in pheochromocytomas -tumors that synthesize and release catecholamines, which are related to various clinical manifestations of the condition. Methods: We measured the concentrations of mRNA coding for the catecholamine-synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), dopamine b-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) and for the catecholamine contents in 12 pheochromocytomas and 12 normal adrenal medullas. Results: The mean content of total catecholamine and the b-actin mRNA expression in the pheochromocytomas were almost the same as those in the normal adrenal medullas. However, the tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas were greater than those of the normal adrenal medullas. Conversely, the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas. These differences are responsible for the difference in the proportions of catecholamines between pheochromocytomas and normal adrenal medullas. The constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in magnitude among the pheochromocytomas, and the tyrosine hydroxylase mRNA expressions correlated with the contents of total catecholamine in the tumors (r=0.964, P<0.0001). Conclusions: These findings indicate that catecholamine production in pheochromocytomas is primarily controlled by the level of gene expression.

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“…It is well established that PACAP can bind to type-1 PACAP receptors in this system, resulting in the stimulation of both adenylyl cyclase activity, with the resultant generation of cAMP, as well as phospholipase C, resulting in the release of Ca 2ϩ via IP 3 and activation of PKC (Rawlings and Hezareh, 1996). Downstream, studies have demonstrated that PACAP can stimulate catecholamine synthesis (via phosphorylation and thus activation of tyrosine hydroxylase) and can stimulate catecholamine secretion (via elevations in intracellular Ca 2ϩ ; Isobe et al, 1994Isobe et al, , 1996O'Farrell and Marley, 1997). The present studies suggest that PACAP can also modulate nicotinic receptor signaling via activation of PKC.…”

Section: Pkc and Ca 2؉ Signaling In Chromaffin Cellsmentioning

confidence: 99%

“…Although there is substantial evidence suggesting that PKC can stimulate catecholamine synthesis, primarily via phosphorylation and thus activation of tyrosine hydroxylase (Rius et al, 1994;Haycock, 1996;Isobe et al, 1996), several studies have suggested that PKC may also modulate nicotinic receptor signaling in the chromaffin cell. In particular, recent studies have demonstrated that pharmacologic activation of PKC using phorbol esters can suppress nicotinic agonist-induced increases in intracellular Ca 2ϩ and downstream catecholamine secretion in both primary cultures of bovine chromaffin cells (Sena et al, 1995;Cox and Parsons, 1997;Sena et al, 1999) and in the PC-12 pheochromocytoma cell line (Harris et al, 1986;Messing et al, 1986;Bouron and Reber, 1994).…”

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confidence: 99%

Modulation of stimulus-secretion coupling in porcine adrenal chromaffin cells by receptor-mediated increases in protein kinase C activity

2000

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Catecholamine (CAT) secretion by adrenal chromaffin cells is primarily triggered by nicotinic receptor-dependent increases in cytosolic Ca(2+). The principal aim of the present study was to determine whether pituitary adenylate cyclase activating peptide (PACAP), which is coreleased with acetylcholine from the splanchnic nerve, can modulate nicotinic receptor-dependent Ca(2+) signaling and catecholamine secretion in porcine adrenal medullary chromaffin (PAMC) cells. Activation of protein kinase C (PKC) with phorbol myristate acetate (PMA) dose- and time-dependently inhibited nicotine (NIC)-induced Ca(2+) transients. At 100 nM PMA, peak Ca(2+) levels were reduced by 27% +/- 2% (P < 0.05) and 41% +/- 3% (P < 0. 05) after 10 and 20 min exposure, respectively. The inhibitory effects of PMA were significantly reduced by preincubation with the PKC inhibitor staurosporine. KCl-induced Ca(2+) transients were also reduced by 20 min PMA treatment (Delta -27% +/- 4%; P < 0.05), suggesting that PKC affects voltage-gated Ca(2+) channel activity. Pretreatment with PACAP also resulted in both time- and concentration-dependent suppression of Ca(2+) transients. After 20 min exposure to 1 microM PACAP, NIC- and KCl-induced transients were reduced by 36% +/- 5% (P < 0.05) and 51% +/- 6% (P < 0.05), respectively. These effects could also be prevented by staurosporine pretreatment. NIC-induced CAT secretion was significantly reduced by pretreatment with both PMA (Delta -56% +/- 2%; P < 0.05) and PACAP (Delta-53% +/- 7%; P < 0.05). This suppressive effect on secretion could be prevented by pretreatment with staurosporine. These data suggest that, in addition to having direct stimulatory effects on catecholamine synthesis and secretion, PACAP can also negatively modulate nicotinic receptor-dependent Ca(2+) signaling and secretion in PAMC cells.

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Cited by 36 publications

References 21 publications

Protein kinase A and protein kinase C signaling pathway interaction in phenylethanolamine N‐methyltransferase gene regulation

Protein kinase A and protein kinase C signaling pathway interaction in phenylethanolamine N‐methyltransferase gene regulation

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas

Modulation of stimulus-secretion coupling in porcine adrenal chromaffin cells by receptor-mediated increases in protein kinase C activity

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