Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lithium stimulated corticotropin (ACTH) secretion by mouse pituitary tumor cells (AtT-20/D16-16) and by normal rat anterior pituitary cells in primary culture. Effects were observed at less than 2 mM LiCl. ACTH secretion was comparable in magnitude to that induced by other secretagogues, was calcium dependent, and was inhibited by somatostatin. Lithium also induced changes in [3H]inositide metabolism; these changes accompanied and were correlated with changes in ACTH secretion. The most prominent and reliable effect was to increase [3H]inositol monophosphate. Other secretagogues had no effect on [3H]inositides in the presence or absence of lithium. Pretreatment with lithium for 3 hr desensitized the cells to the effects of subsequent exposure to lithium. The cells were not desensitized to lithium by pretreatment with other secretagogues, nor were they desensitized by lithium to the effects of corticotropin-releasing factor, high potassium, or forskolin. However, pretreatment with lithium did desensitize the cells to stimulation by phorbol esters. The interaction between lithium and phorbol esters suggests the involvement of inositide metabolism and protein kinase C in the regulation of ACTH secretion and possibly of other hormones or neurotransmitters. It also suggests new avenues of research into the basis of lithium's psychopharmacological effects.
 ...
PMID:Lithium induces corticotropin secretion and desensitization in cultured anterior pituitary cells. 298 36

The hypophysiotrophic hormone corticotropin releasing factor (CRF) stimulates the anterior pituitary corticotroph to export stress hormones such as adrenocorticotrophic hormone (ACTH). In rat anterior pituitary cells, CRF-induced elevation of cyclic AMP was profoundly potentiated (by an order of magnitude) by stimulators of protein kinase C. This effect occurred within minutes, was concentration dependent, and exhibited the appropriate pharmacological specificity to attribute the effects to protein kinase C. Phorbol myristate acetate (PMA), phorbol dibutyrate (PDB) and teleocidin were active with appropriate EC50's, while 4-alpha-PMA was inactive. PMA and PDB were also ACTH secretagogues in their own right. We suggest that protein kinase C can modulate CRF receptor coupling to the adenylate cyclase holoenzyme in anterior pituitary cells.
 ...
PMID:Protein kinase C potentiates corticotropin releasing factor stimulated cyclic AMP in pituitary. 309 70

The BE(2)-M17 and BE(2)-C human neuroblastoma cell lines have been shown to synthesize and secrete corticotropin-releasing factor (CRF) following retinoic acid treatment. It has been demonstrated that CRF secretion and intracellular synthesis increases in response to forskolin treatment. In this report, we have further characterized these cells in response to protein kinase C activators, dexamethasone, interleukin-1 alpha, as well as various neurotransmitters and peptides. Nanomolar concentrations of the phorbol ester--phorbol 12 myristate 13--acetate (TPA), increased intracellular CRF content in both cell lines while increasing secretion only in the BE(2)-M17 cell. Nanomolar concentrations of dexamethasone were not able to alter basal levels of secretion and content in either cell type. However, in the BE(2)-M17 cell but not the BE(2)-C cell, the same concentrations of dexamethasone added to 30 microM forskolin augmented levels of CRF secretion and content. Likewise, the same augmented response in CRF secretion and content was seen only in the BE(2)-M17 cell line when nanomolar concentrations of dexamethasone were added to 20 nM TPA. Furthermore, only in the BE(2)-M17 cell line were micromolar levels of the biogenic amine serotonin able to increase levels of CRF secretion and content. No effects on CRF in both cell lines were demonstrable with picomolar levels of interleukin-1 alpha as well as micromolar levels of acetylcholine, norepinephrine, arginine-vasopressin, oxytocin, and angiotensin-II. The potential usefulness of these cells as models of central nervous system or placental CRF-containing neurons is discussed.
 ...
PMID:Regulation of corticotropin-releasing factor secretion and synthesis in the human neuroblastoma clones- BE(2)-M17 and BE(2)-C. 755 Feb 93

Corticotropin-releasing hormone (CRH) is believed to have a role as an important brain neuroregulator acting through specific receptors coupled to adenylate cyclase in addition to its major role in regulating pituitary adrenocorticotropin synthesis and secretion. To study the potential modulatory effects of various regulators and the central effects of CRH, we studied the effects of phorbol ester myristate acetate (PMA), arginine vasopressin (AVP), corticosterone, dexamethasone, and progesterone on CRH stimulation of cyclic adenosine monophosphate (cAMP) production in extrahypothalamic forebrain cell cultures derived from day 17 gestation fetal rats. These cultures contain CRH receptors with similar characteristics as those in anterior pituitary and brain. CRH (10(-9) - 10(-7) M) stimulated cAMP in a dose-dependent fashion and maximal stimulation was clearly seen at 10(-7) M CRH. Incubation of the cells with PMA (10(-7) M), a protein kinase C (PKC) agonist, had no effect on basal cAMP, but potentiated CRH-stimulated cAMP. AVP (10(-8), 10(-7) M) had no effect on basal nor CRH-stimulated cAMP accumulation. Corticosterone (10(-7), 10(-6) M) or dexamethasone (10(-9) - 10(-7) M) pre-incubation for 18 h did not diminish basal cAMP levels nor inhibit CRH-induced stimulation of cAMP. However, corticosterone inhibited CRH-induced cAMP production in anterior pituitary cells. Neither did exposure to progesterone (2 x 10(-8) M) modulate basal cAMP, CRH-induced cAMP production nor the potentiation of CRH stimulation by PMA. The data demonstrate that CRH receptors in dissociated fetal extrahypothalamic forebrain cell cultures are coupled to an adenylyl cyclase/cAMP second messenger system similarly as shown in studies with anterior pituitary membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modulation of corticotropin-releasing hormone stimulated cyclic adenosine monophosphate production by brain cells. 762 Aug 89

Corticotropin-releasing factor (CRF) has been shown to attenuate vascular leakage in injured skin, mucous membrane, muscle, lung, and brain. We previously reported that CRF increases cytosolic free calcium concentrations ([Ca2+]i), cellular cAMP, and inositol trisphosphates in human epidermoid A-431 cells. This study identified protein kinase C isoforms in A-431 cells and investigated the effect of CRF on PKC activity and isoform translocation. PKC alpha, beta, gamma, delta, and zeta isoforms were present in cytosolic and membrane fractions, but the epsilon isoform was detected only in the membrane fraction. Exposure of cells to CRF at 420 pM for 1 min increased PKC activity and led to the translocation of PKC alpha and beta isoforms from cytosol to membrane. The translocation was dependent on an increase in [Ca2+]i, because cells treated with 100 microM BAPTA-am (an intracellular Ca2+ chelator), then exposed to CRF, showed neither increases in PKC activity nor translocation of PKC isoforms. This suggests that a CRF-induced increase in [Ca2+]i mediates the increase in PKC activity.
 ...
PMID:Corticotropin-releasing factor increases protein kinase C activity by elevating membrane-bound alpha and beta isoforms. 770 72

Interleukin-1 (IL1) is a key messenger implicated in endocrine and immune systems that interact to mediate the stress response. Corticotropin-releasing factor (CRF) secretion and synthesis in the NPLC-KC human hepatoma cell line has been shown to respond to IL1 stimulation. We have studied how various inhibitors of second messenger pathways alter this IL1 effect. NPLC-KC cells were grown in six-well Costar plates and treated for 12 or 24 h with or without 500 pM IL1 (alpha form) in the presence of various inhibitors of second messenger pathways. Inhibitors included the protein kinase C (PKC) inhibitor, H-7; the protein kinase A inhibitor, IP20; or the cyclooxygenase inhibitor indomethacin (IND). Both cell extracts and secretion media were assayed for CRF-like immunoreactivity by radioimmunoassay. IP20, H-7, and IND all reduced basal CRF secretion at 24 h but not at 12 h. No effects were seen on basal CRF synthesis with these inhibitors. The three inhibitors also reduced IL1 effects on CRF secretion at 12 and 24 h. The reduction seen with all three inhibitors was statistically significant (P < 0.05) at 12 h. Although a reduction was seen with all three inhibitors at 24 h, a statistically significant reduction (P < 0.05) was demonstrable only for H-7. IL1 stimulated CRF synthesis in the NPLC-KC cells appears to only involve PKC pathways. Only the PKC inhibitor H-7 reduced the augmentation that IL1 produces on CRF synthesis. This effect was statistically significant at 12 and 24 h (P < 0.05).
 ...
PMID:Interleukin-1 alpha induces corticotropin-releasing factor secretion and synthesis from NPLC-KC cells through various second messenger pathways. 788 28

This study was undertaken to determine the roles of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the regulation of adrenocorticotropin (ACTH) secretion in perfused ovine anterior pituitary (AP) cells and their ability to cause protein phosphorylation and dephosphorylation in these cells. Freshly dispersed ovine AP cells were maintained in a miniperifusion chamber and ACTH secretion was monitored every 20 s. When cells were perfused with CRF (1 nM, 5 min) or AVP (1 nM, 5 min), ACTH release was increased 20-fold and 12-fold, respectively. When an ovine AP cell membrane fraction was incubated with either CRF or AVP, CRF stimulated the phosphorylation of at least 11 proteins and the dephosphorylation of at least 5 phosphoproteins, whereas AVP caused the phosphorylation of at least 15 proteins and the dephosphorylation of 5 proteins. A comparison of the proteins phosphorylated by CRF or AVP with those phosphorylated by cAMP or protein kinase C activators suggested that the hormone-stimulated phosphorylation may also involve unidentified protein kinases. Additionally, at least eight proteins appeared to be phosphorylated by both CRF and AVP. Furthermore, in the case of four particular proteins both CRF and AVP stimulated phosphorylation at low concentrations of Ca2+ (0.1-1 microM), but at high concentrations of Ca2+ (10-100 microM) CRF or AVP triggered dephosphorylation of these proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Studies of the mechanisms of action of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the ovine anterior pituitary: evidence that CRF and AVP stimulate protein phosphorylation and dephosphorylation. 789 15

Corticotropin-releasing factor (CRF), the key neuropeptide in the stress cascade, has major inhibitory actions on testicular function in addition to its known antireproductive effects at the central level (inhibition of sexual behavior and LH secretion). CRF is secreted by the Leydig cells of the testis and acts through high-affinity receptors at the Leydig cell membrane as a potent negative regulator of LH action, inhibiting gonadotropin-induced cAMP generation and androgen production. CRF is also a primary stimulus of beta-endorphin secretion by the Leydig cells, which in turn exerts paracrine inhibition of FSH action in the tubular compartment of the testis through high-affinity receptors in the Sertoli cells. CRF action in the Leydig cells involves a pertussis toxin-insensitive guanyl nucleotide regulatory unit. In contrast to CRF receptors in the brain, pituitary, and other peripheral tissues, those in the Leydig cell are not coupled to Gs. The inhibitory action of CRF in the Leydig cell is exerted through protein kinase C, at the level of the catalytic subunit of adenylate cyclase. The secretion of CRF by the Leydig cell is stimulated by LH, acting via release of serotonin (5HT) and autocrine activation of 5HT2 receptors. Serotonin acts on 5HT2 receptors in the Leydig cell to stimulate CRF secretion via a pertussis toxin insensitive G-protein and presumably through activation of phosphoinositide hydrolysis. The diversity of the biochemical responses to CRF and 5HT2 receptor activation (i.e., inhibition of adenylate cyclase at the cytoplasmic aspect of the cell membrane vs. stimulation of CRF release from secretion granules) may reflect the stimulation of different protein kinase C isoenzymes. The LH-->5HT-->CRF inhibitory loop serves to continuously buffer the stimulation of androgen production by gonadotropin. 5HT, the immediate stimulus of testicular CRF secretion, is released during stress and is locally increased in the testis in pathological conditions associated with impaired testicular function (i.e., orchitis, varicocele). Also, propranolol, the beta-adrenergic antagonist frequently used in the control of blood pressure in patients with hypertension and often associated with impotence, acts via a serotonergic mechanism to stimulate CRF secretion and causes marked inhibition of LH-induced cAMP production and steroidogenesis in cultured Leydig cells. These basic studies of 5HT and CRF are relevant to the pathogenesis of testicular dysfunction and for the development of antagonist therapies to block CRF production and its local antireproductive effects.
 ...
PMID:Corticotropin-releasing factor: an antireproductive hormone of the testis. 838 38

The immunomodulating properties of a neuropeptide hormone, corticotropin-releasing factor (CRF), led us to investigate its effect on cAMP production by human peripheral blood mononuclear cells (MNC). In response to stimulation with CRF (100 nM), a statistically significant (P = 0.019) increase occurred in the amount of cAMP produced by MNC. Purified monocytes, but not lymphocytes, also displayed a significant (P = 0.01) increase (8- to 10-fold) in intracellular cAMP after treatment with CRF (100 nM). The antagonist alpha-helical CRF9-41 (100 nM) counteracted the cAMP increase induced by CRF (100 nM). The CRF-induced cAMP production was augmented by pretreatment of MNC with a cAMP-dependent protein kinase (PKA) peptide inhibitor (PI20), but was virtually unaffected by the protein kinase C (PKC) inhibitor H7, suggesting a role for cAMP signalling. Moreover, the CRF-stimulated cAMP level was reduced to baseline by intracellular Ca2+ antagonist HA1004, indicating a role for Ca(2+)-signalling. Based on these findings, it is concluded that cAMP and/or Ca2+ play a second messenger role in the CRF signal transduction pathway.
 ...
PMID:Corticotropin-releasing factor-induced production of cyclic AMP by human peripheral blood immunocytes. 839 Apr

In an attempt to determine if PACAP synergistically interacts with vasopressin (VP) and protein kinase C (PKC) to enhance cyclic AMP formation and adrenocorticotrophic hormone (ACTH) secretion, the effects of PACAP, either alone or together with VP and the phorbol ester phorbol 12-myristate 13-acetate (PMA) were examined in primary cultures of rat anterior pituitary cells. VP failed to potentiate the stimulatory effect of PACAP on cyclic AMP formation, while it dramatically enhanced the effect of corticotropin-releasing factor (CRF). However, activation of PKC upon exposure of cells to PMA amplified cyclic AMP production induced by both peptides, though in the case of PACAP, contrary to that of CRF, potentiation was markedly dependent on the blockade of phosphodiesterase (PDE) activity, for it was undetectable in the absence of the inhibitor Rolipram. Depletion of PKC by long-term treatment of pituitary cells with PMA abolished the synergistic influence of PMA. There was no significant effect of PACAP, either alone or together with PMA, on ACTH secretion, while PMA enhanced peptide secretion elicited by CRF. The data show that in anterior pituitary cells cyclic AMP accumulation induced by PACAP and CRF was differentially modulated by PKC and PDE activities and that the potentiation of PACAP-stimulated cyclic AMP accumulation by PMA was not reflected by parallel increment of ACTH secretion.
 ...
PMID:Vasopressin, unlike phorbol ester, fails to synergistically interact with pituitary adenylate cyclase activating polypeptide (PACAP) in stimulating cyclic AMP formation and ACTH secretion in cultured anterior pituitary cells. 839 88


<< Previous 1 2 3 4 5 6 7 Next >>